Kit, device, and method for detecting lung cancer

Abstract

This application provides a kit or a device for detection of lung cancer, comprising a nucleic acid(s) for detecting a miRNA(s) in a sample from a subject, and a method for detecting lung cancer, comprising measuring the miRNA(s) in vitro.

Claims

1. A method for detecting and treating or performing a diagnostic procedure for lung cancer, comprising: determining an expression level of hsa-miR-2467-3p in a sample from a human subject using a nucleic acid(s) capable of specifically binding to hsa-miR-2467-3p, or using a kit or device comprising a nucleic acid(s) capable of specifically binding to hsa-miR-2467-3p, wherein the determining comprises the following steps of: (a) contacting hsa-miR-2467-3p in the sample or complementary polynucleotide(s) thereof prepared from hsa-miR-2467-3p with the nucleic acid(s); (b) measuring an expression level of hsa-miR-2467-3p; (c) comparing the expression level of hsa-miR-2467-3p measured in the step (b) to a control expression level of hsa-miR-2467-3p in a control sample from a healthy human subject measured in the same way as in the step (b) to allow for diagnosis of lung cancer; (d) detecting an increased level of hsa-miR-2467-3p in the sample from the human subject as compared to the control expression level of hsa-miR-2467-3p from the sample from the human subject that does not have lung cancer, wherein the increased level of hsa-miR-2467-3p indicates that the human subject has lung cancer; and (e) treating the human subject having lung cancer or performing a diagnostic procedure on the human subject having lung cancer; wherein the sample is blood, serum, or plasma; wherein the treatment comprises chemotherapy, radiotherapy, immunotherapy, molecular targeted therapy, surgery or a combination thereof; and wherein the diagnostic procedure comprises an imaging test method selected from the group consisting of a chest X-ray examination, CT examination, MRI examination, and PET examination; a pathological examination method selected from the group consisting of sputum cytology, pleural fluid analysis, bronchoscopy, and percutaneous needle biopsy; or a combination thereof.

2. The method according to claim 1, wherein the nucleic acid(s) is a polynucleotide(s) selected from the group consisting of the following polynucleotides (a) to (e): (a) a polynucleotide consisting of a nucleotide sequence of SEQ ID NO: 22, or a nucleotide sequence derived from the nucleotide sequence in which the nucleic acid u is replaced with t, a variant thereof, a derivative thereof, or a fragment thereof comprising 15 or more consecutive nucleotides; (b) a polynucleotide comprising a nucleotide sequence of SEQ ID NO: 22; (c) a polynucleotide consisting of a nucleotide sequence complementary to a nucleotide sequence of SEQ ID NO: 22, or a nucleotide sequence derived from the nucleotide sequence in which the nucleic acid u is replaced with t, a variant thereof, a derivative thereof, or a fragment thereof comprising 15 or more consecutive nucleotides; (d) a polynucleotide comprising a nucleotide sequence complementary to a nucleotide sequence of SEQ ID NO: 22, or a nucleotide sequence derived from the nucleotide sequence in which the nucleic acid u is replaced with t; and (e) a polynucleotide hybridizing under stringent conditions to any of the polynucleotides (a) to (d).

3. The method according to claim 1, wherein the method further comprises: determining an expression level(s) of one or more other miRNA(s) selected from the following other lung cancer markers: miR-6787-5p, miR-920, miR-3622a-5p, miR-1185-1-3p, miR-4327, miR-5739, miR-937-5p, miR-1181, miR-1185-2-3p, miR-1193, miR-1207-5p, miR-1238-5p, miR-1246, miR-1249-5p, miR-1292-3p, miR-1469, miR-1470, miR-197-5p, miR-208a-5p, miR-2110, miR-211-3p, miR-3122, miR-3141, miR-3156-5p, miR-3158-5p, miR-3160-5p, miR-3180-3p, miR-3191-3p, miR-3194-3p, miR-320b, miR-328-5p, miR-3610, miR-3619-3p, miR-3620-5p, miR-370-3p, miR-373-5p, miR-3917, miR-3937, miR-4259, miR-4281, miR-4294, miR-4419b, miR-4428, miR-4429, miR-4433a-3p, miR-4447, miR-4449, miR-4459, miR-4480, miR-4485-5p, miR-4486, miR-4488, miR-4489, miR-4505, miR-4513, miR-4515, miR-4530, miR-4535, miR-4635, miR-4640-5p, miR-4646-5p, miR-4656, miR-4663, miR-4665-5p, miR-4706, miR-4707-5p, miR-4708-3p, miR-4710, miR-4718, miR-4722-5p, miR-4727-3p, miR-4730, miR-4734, miR-4740-5p, miR-4747-3p, miR-4749-5p, miR-4755-3p, miR-4763-5p, miR-4787-3p, miR-5008-5p, miR-5010-5p, miR-504-3p, miR-5090, miR-5100, miR-5196-5p, miR-551b-5p, miR-557, miR-5787, miR-6090, miR-6124, miR-6132, miR-6510-5p, miR-6511b-5p, miR-6515-3p, miR-654-5p, miR-658, miR-668-5p, miR-6722-5p, miR-6724-5p, miR-6729-3p, miR-6737-5p, miR-6756-5p, miR-6762-5p, miR-6763-3p, miR-6766-5p, miR-6769a-5p, miR-6771-5p, miR-6786-5p, miR-6789-5p, miR-6794-5p, miR-6796-3p, miR-6797-5p, miR-6800-3p, miR-6802-5p, miR-6803-5p, miR-6805-3p, miR-6805-5p, miR-6807-5p, miR-6812-5p, miR-6819-5p, miR-6822-5p, miR-6824-5p, miR-6826-5p, miR-6850-5p, miR-6858-5p, miR-6861-5p, miR-6880-3p, miR-7107-5p, miR-7109-5p, miR-7114-5p, miR-7704, miR-7846-3p, miR-8052, miR-8060, miR-8071, miR-8073, miR-874-5p, miR-204-3p, miR-3154, miR-3960, miR-4433a-5p, miR-4455, miR-4462, miR-4476, miR-4508, miR-4687-3p, miR-4687-5p, miR-4732-5p, miR-4771, miR-642a-3p, miR-6732-5p, miR-6760-5p, miR-6799-5p, miR-6820-5p, miR-6821-5p, miR-6829-5p, miR-6893-5p, miR-7108-3p, miR-7111-5p, miR-8089, miR-885-3p, miR-92b-3p, miR-1343-3p, miR-6746-5p, miR-422a, miR-187-5p, miR-4632-5p, miR-6791-5p, miR-103a-3p, miR-107, miR-1199-5p, miR-1225-3p, miR-1225-5p, miR-1228-5p, miR-1229-5p, miR-1233-5p, miR-1237-5p, miR-1247-3p, miR-1249-3p, miR-1254, miR-1260b, miR-1268a, miR-1268b, miR-1273g-3p, miR-128-1-5p, miR-128-2-5p, miR-1290, miR-150-3p, miR-17-3p, miR-1908-5p, miR-1909-3p, miR-1914-3p, miR-1915-3p, miR-191-5p, miR-22-3p, miR-23b-3p, miR-24-3p, miR-296-3p, miR-296-5p, miR-3131, miR-3162-5p, miR-3188, miR-3196, miR-3197, miR-320a, miR-342-5p, miR-3621, miR-3648, miR-3656, miR-365a-5p, miR-3665, miR-3679-5p, miR-371a-5p, miR-3940-5p, miR-423-5p, miR-4257, miR-4270, miR-4271, miR-4286, miR-4298, miR-4417, miR-4442, miR-4446-3p, miR-4448, miR-4454, miR-4467, miR-4472, miR-4507, miR-4516, miR-451a, miR-4649-5p, miR-4651, miR-4665-3p, miR-4674, miR-4675, miR-4689, miR-4695-5p, miR-4697-5p, miR-4725-3p, miR-4739, miR-4745-5p, miR-4763-3p, miR-4792, miR-486-3p, miR-5001-5p, miR-5195-3p, miR-550a-5p, miR-5698, miR-6075, miR-6088, miR-6089, miR-6125, miR-6126, miR-614, miR-615-5p, miR-619-5p, miR-638, miR-642b-3p, miR-650, miR-663a, miR-663b, miR-6717-5p, miR-6721-5p, miR-6726-5p, miR-6727-5p, miR-6738-5p, miR-6741-5p, miR-6749-5p, miR-6752-5p, miR-675-5p, miR-6757-5p, miR-6763-5p, miR-6765-5p, miR-6775-5p, miR-6780b-5p, miR-6782-5p, miR-6784-5p, miR-6800-5p, miR-6806-5p, miR-6840-3p, miR-6848-5p, miR-6851-5p, miR-6870-5p, miR-6872-3p, miR-6875-5p, miR-6877-5p, miR-6879-5p, miR-6880-5p, miR-6885-5p, miR-6887-5p, miR-7108-5p, miR-711, miR-7113-3p, miR-744-5p, miR-760, miR-7845-5p, miR-7847-3p, miR-7977, miR-8059, miR-8063, miR-8072, miR-874-3p, miR-92a-2-5p, miR-92b-5p, miR-940, miR-1228-3p, miR-1275, miR-1307-3p, miR-1343-5p, miR-23a-3p, miR-29b-3p, miR-3135b, miR-3185, miR-4532, miR-4690-5p, miR-4758-5p, miR-4783-3p, miR-6131, miR-625-3p, miR-6511a-5p, miR-6765-3p, miR-6816-5p, miR-6825-5p, miR-6845-5p, miR-7150, miR-7641, miR-7975, and miR-92a-3p, or to a complementary strand of the polynucleotide, in the sample from the human subject by the same way as in the steps (a) and (b) using a nucleic acid(s) capable of specifically binding to the miRNA(s), or using a kit or device comprising a nucleic acid(s) capable of specifically binding to the miRNA(s).

4. The method according to claim 1, wherein the measuring in the step (b) is performed by quantitative RT-PCR using the nucleic acid(s) as primer(s).

5. The method according to claim 1, wherein the measuring in the step (b) is performed by hybridization using the nucleic acid(s) as probe(s).

6. The method according to claim 3, wherein the measuring in the step (b) is performed by quantitative RT-PCR using the nucleic acid(s) as primer(s).

7. The method according to claim 3, wherein the measuring in the step (b) is performed by hybridization using the nucleic acid(s) as probe(s).

Description

BRIEF DESCRIPTION OF THE DRAWINGS

(1) FIG. 1 This figure shows the relationship between the nucleotide sequences of hsa-miR-4433a-5p represented by SEQ ID NO: 142 and hsa-miR-4433a-3p represented by SEQ ID NO: 46, which are produced from the precursor hsa-mir-4433a represented by SEQ ID NO: 382.

(2) FIG. 2 Upper panel: a discriminant (0.960×hsa-miR-1343-3p-0.703×hsa-miR-197-5p-0.184×hsa-miR-6741-5p+0.506×hsa-miR-4687-3p-0.471×hsa-miR-1268b-1.273) was prepared by use of Fisher's discriminant analysis from the measured expression level values of hsa-miR-1343-3p (SEQ ID NO: 164), hsa-miR-197-5p (SEQ ID NO: 18), hsa-miR-6741-5p (SEQ ID NO: 268), hsa-miR-4687-3p (SEQ ID NO: 147), and hsa-miR-1268b (SEQ ID NO: 184) in sera of test subjects without lung cancer (total 2,777 people including 1,233 healthy subjects, 263 benign bone and soft tissue tumor patients and benign breast disease patients, 1,281 patients having a cancer other than lung cancer) and lung cancer patients (1,186 people) selected as a training cohort, and discriminant scores obtained from the discriminant were plotted on the ordinate against the sample groups on the abscissa. In consideration of easy viewability of the figure, the discriminant scores are shown as to 400 people each extracted at random from the test subjects without lung cancer and the patients with lung cancer. The dotted line in the panel depicts a discriminant boundary that offered a discriminant score of 0 and discriminated between the two groups. Lower panel: discriminant scores obtained from assignment to the discriminant (0.960×hsa-miR-1343-3p-0.703×hsa-miR-197-5p-0.184×hsa-miR-6741-5p+0.506×hsa-miR-4687-3p-0.471×hsa-miR-1268b-1.273) prepared from the training cohort as to the measured expression level values of hsa-miR-1343-3p (SEQ ID NO: 164), hsa-miR-197-5p (SEQ ID NO: 18), hsa-miR-6741-5p (SEQ ID NO: 268), hsa-miR-4687-3p (SEQ ID NO: 147), and hsa-miR-1268b (SEQ ID NO: 184) in sera of test subjects without lung cancer (total 1,191 people including 567 healthy subjects, 105 benign bone and soft tissue tumor patients and benign breast disease patients, 519 patients having a cancer other than lung cancer) and lung cancer patients (508 people) selected as a validation cohort were plotted on the ordinate against the sample groups on the abscissa. In consideration of easy viewability of the figure, the discriminant scores are shown as to 400 people each extracted at random from the test subjects without lung cancer and the patients with lung cancer. The dotted line in the panel depicts the discriminant boundary that offered a discriminant score of 0 and discriminated between the two groups.

(3) FIG. 3 Upper panel: the discriminant scores of the validation cohort described above are categorized on the basis of the healthy subjects and each histological type of lung cancer (small cell carcinoma, adenocarcinoma, squamous cell carcinoma, large cell carcinoma, and other lung cancers). The dotted line in the panel depicts the discriminant boundary that offered a discriminant score of 0 and discriminated between the two groups. Lower panel: the discriminant scores of the validation cohort described above are categorized on the basis of the healthy subjects and the progressive stages of lung cancer (stage I, stage II, and stage III/IV (stage III and stage IV)). The dotted line in the panel depicts the discriminant boundary that offered a discriminant score of 0 and discriminated between the two groups.

MODES FOR CARRYING OUT THE INVENTION

(4) Hereinafter, the present invention will be further described in detail.

(5) 1. Target Nucleic Acid for Lung Cancer

(6) Primary target nucleic acids, as lung cancer markers, for detecting the presence and/or absence of lung cancer or lung cancer cells using the nucleic acids such as the nucleic acid probes or the primers for detection of lung cancer defined above according to the present invention comprise at least one miRNA selected from the group consisting of the following miRNAs: miR-6787-5p, miR-920, miR-3622a-5p, miR-1185-1-3p, miR-4327, miR-5739, miR-937-5p, miR-1181, miR-1185-2-3p, miR-1193, miR-1207-5p, miR-1238-5p, miR-1246, miR-1249-5p, miR-1292-3p, miR-1469, miR-1470, miR-197-5p, miR-208a-5p, miR-2110, miR-211-3p, miR-2467-3p, miR-3122, miR-3141, miR-3156-5p, miR-3158-5p, miR-3160-5p, miR-3180-3p, miR-3191-3p, miR-3194-3p, miR-320b, miR-328-5p, miR-3610, miR-3619-3p, miR-3620-5p, miR-370-3p, miR-373-5p, miR-3917, miR-3937, miR-4259, miR-4281, miR-4294, miR-4419b, miR-4428, miR-4429, miR-4433a-3p, miR-4447, miR-4449, miR-4459, miR-4480, miR-4485-5p, miR-4486, miR-4488, miR-4489, miR-4505, miR-4513, miR-4515, miR-4530, miR-4535, miR-4635, miR-4640-5p, miR-4646-5p, miR-4656, miR-4663, miR-4665-5p, miR-4706, miR-4707-5p, miR-4708-3p, miR-4710, miR-4718, miR-4722-5p, miR-4727-3p, miR-4730, miR-4734, miR-4740-5p, miR-4747-3p, miR-4749-5p, miR-4755-3p, miR-4763-5p, miR-4787-3p, miR-5008-5p, miR-5010-5p, miR-504-3p, miR-5090, miR-5100, miR-5196-5p, miR-551b-5p, miR-557, miR-5787, miR-6090, miR-6124, miR-6132, miR-6510-5p, miR-6511b-5p, miR-6515-3p, miR-654-5p, miR-658, miR-668-5p, miR-6722-5p, miR-6724-5p, miR-6729-3p, miR-6737-5p, miR-6756-5p, miR-6762-5p, miR-6763-3p, miR-6766-5p, miR-6769a-5p, miR-6771-5p, miR-6786-5p, miR-6789-5p, miR-6794-5p, miR-6796-3p, miR-6797-5p, miR-6800-3p, miR-6802-5p, miR-6803-5p, miR-6805-3p, miR-6805-5p, miR-6807-5p, miR-6812-5p, miR-6819-5p, miR-6822-5p, miR-6824-5p, miR-6826-5p, miR-6850-5p, miR-6858-5p, miR-6861-5p, miR-6880-3p, miR-7107-5p, miR-7109-5p, miR-7114-5p, miR-7704, miR-7846-3p, miR-8052, miR-8060, miR-8071, miR-8073, miR-874-5p, miR-204-3p, miR-3154, miR-3960, miR-4433a-5p, miR-4455, miR-4462, miR-4476, miR-4508, miR-4687-3p, miR-4687-5p, miR-4732-5p, miR-4771, miR-642a-3p, miR-6732-5p, miR-6760-5p, miR-6799-5p, miR-6820-5p, miR-6821-5p, miR-6829-5p, miR-6893-5p, miR-7108-3p, miR-7111-5p, miR-8089, miR-885-3p, and miR-92b-3p, or a polynucleotide complementary to the miRNA. Furthermore, at least one miRNA selected from the group consisting of the following other lung cancer markers that can be combined with these miRNAs, i.e., miR-1343-3p, miR-6746-5p, miR-422a, miR-187-5p, miR-4632-5p, miR-6791-5p, miR-103a-3p, miR-107, miR-1199-5p, miR-1225-3p, miR-1225-5p, miR-1228-5p, miR-1229-5p, miR-1233-5p, miR-1237-5p, miR-1247-3p, miR-1249-3p, miR-1254, miR-1260b, miR-1268a, miR-1268b, miR-1273g-3p, miR-128-1-5p, miR-128-2-5p, miR-1290, miR-150-3p, miR-17-3p, miR-1908-5p, miR-1909-3p, miR-1914-3p, miR-1915-3p, miR-191-5p, miR-22-3p, miR-23b-3p, miR-24-3p, miR-296-3p, miR-296-5p, miR-3131, miR-3162-5p, miR-3188, miR-3196, miR-3197, miR-320a, miR-342-5p, miR-3621, miR-3648, miR-3656, miR-365a-5p, miR-3665, miR-3679-5p, miR-371a-5p, miR-3940-5p, miR-423-5p, miR-4257, miR-4270, miR-4271, miR-4286, miR-4298, miR-4417, miR-4442, miR-4446-3p, miR-4448, miR-4454, miR-4467, miR-4472, miR-4507, miR-4516, miR-451a, miR-4649-5p, miR-4651, miR-4665-3p, miR-4674, miR-4675, miR-4689, miR-4695-5p, miR-4697-5p, miR-4725-3p, miR-4739, miR-4745-5p, miR-4763-3p, miR-4792, miR-486-3p, miR-5001-5p, miR-5195-3p, miR-550a-5p, miR-5698, miR-6075, miR-6088, miR-6089, miR-6125, miR-6126, miR-614, miR-615-5p, miR-619-5p, miR-638, miR-642b-3p, miR-650, miR-663a, miR-663b, miR-6717-5p, miR-6721-5p, miR-6726-5p, miR-6727-5p, miR-6738-5p, miR-6741-5p, miR-6749-5p, miR-6752-5p, miR-675-5p, miR-6757-5p, miR-6763-5p, miR-6765-5p, miR-6775-5p, miR-6780b-5p, miR-6782-5p, miR-6784-5p, miR-6800-5p, miR-6806-5p, miR-6840-3p, miR-6848-5p, miR-6851-5p, miR-6870-5p, miR-6872-3p, miR-6875-5p, miR-6877-5p, miR-6879-5p, miR-6880-5p, miR-6885-5p, miR-6887-5p, miR-7108-5p, miR-711, miR-7113-3p, miR-744-5p, miR-760, miR-7845-5p, miR-7847-3p, miR-7977, miR-8059, miR-8063, miR-8072, miR-874-3p, miR-92a-2-5p, miR-92b-5p, miR-940, miR-1228-3p, miR-1275, miR-1307-3p, miR-1343-5p, miR-23a-3p, miR-29b-3p, miR-3135b, miR-3185, miR-4532, miR-4690-5p, miR-4758-5p, miR-4783-3p, miR-6131, miR-625-3p, miR-6511a-5p, miR-6765-3p, miR-6816-5p, miR-6825-5p, miR-6845-5p, miR-7150, miR-7641, miR-7975, and miR-92a-3p, or a polynucleotide complementary to the miRNA can also be preferably used as target nucleic acids.

(7) These miRNAs include, for example, a human gene comprising a nucleotide sequence represented by any of SEQ ID NOs: 1 to 329 (i.e., miR-6787-5p, miR-920, miR-3622a-5p, miR-1185-1-3p, miR-4327, miR-5739, miR-937-5p, miR-1181, miR-1185-2-3p, miR-1193, miR-1207-5p, miR-1238-5p, miR-1246, miR-1249-5p, miR-1292-3p, miR-1469, miR-1470, miR-197-5p, miR-208a-5p, miR-2110, miR-211-3p, miR-2467-3p, miR-3122, miR-3141, miR-3156-5p, miR-3158-5p, miR-3160-5p, miR-3180-3p, miR-3191-3p, miR-3194-3p, miR-320b, miR-328-5p, miR-3610, miR-3619-3p, miR-3620-5p, miR-370-3p, miR-373-5p, miR-3917, miR-3937, miR-4259, miR-4281, miR-4294, miR-4419b, miR-4428, miR-4429, miR-4433a-3p, miR-4447, miR-4449, miR-4459, miR-4480, miR-4485-5p, miR-4486, miR-4488, miR-4489, miR-4505, miR-4513, miR-4515, miR-4530, miR-4535, miR-4635, miR-4640-5p, miR-4646-5p, miR-4656, miR-4663, miR-4665-5p, miR-4706, miR-4707-5p, miR-4708-3p, miR-4710, miR-4718, miR-4722-5p, miR-4727-3p, miR-4730, miR-4734, miR-4740-5p, miR-4747-13p, miR-4749-5p, miR-4755-3p, miR-4763-5p, miR-4787-3p, miR-5008-5p, miR-5010-5p, miR-504-3p, miR-5090, miR-5100, miR-5196-5p, miR-551b-5p, miR-557, miR-5787, miR-6090, miR-6124, miR-6132, miR-6510-5p, miR-6511b-5p, miR-6515-3p, miR-654-5p, miR-658, miR-668-5p, miR-6722-5p, miR-6724-5p, miR-6729-3p, miR-6737-5p, miR-6756-5p, miR-6762-5p, miR-6763-3p, miR-6766-5p, miR-6769a-5p, miR-6771-5p, miR-6786-5p, miR-6789-5p, miR-6794-5p, miR-6796-3p, miR-6797-5p, miR-6800-3p, miR-6802-5p, miR-6803-5p, miR-6805-3p, miR-6805-5p, miR-6807-5p, miR-6812-5p, miR-6819-5p, miR-6822-5p, miR-6824-5p, miR-6826-5p, miR-6850-5p, miR-6858-5p, miR-6861-5p, miR-6880-3p, miR-7107-5p, miR-7109-5p, miR-7114-5p, miR-7704, miR-7846-3p, miR-8052, miR-8060, miR-8071, miR-8073, miR-874-5p, miR-204-3p, miR-3154, miR-3960, miR-4433a-5p, miR-4455, miR-4462, miR-4476, miR-4508, miR-4687-3p, miR-4687-5p, miR-4732-5p, miR-4771, miR-642a-3p, miR-6732-5p, miR-6760-5p, miR-6799-5p, miR-6820-5p, miR-6821-5p, miR-6829-5p, miR-6893-5p, miR-7108-3p, miR-7111-5p, miR-8089, miR-885-3p, miR-92b-3p, miR-13413-13p, miR-6746-5p, miR-422a, miR-187-5p, miR-4632-5p, miR-6791-5p, miR-103a-3p, miR-107, miR-1199-5p, miR-1225-3p, miR-1225-5p, miR-1228-5p, miR-1229-5p, miR-1233-5p, miR-1237-5p, miR-1247-3p, miR-1249-3p, miR-1254, miR-1260b, miR-1268a, miR-1268b, miR-1273g-3p, miR-128-1-5p, miR-128-2-5p, miR-1290, miR-150-3p, miR-17-3p, miR-1908-5p, miR-1909-3p, miR-1914-3p, miR-1915-3p, miR-191-5p, miR-22-3p, miR-23b-3p, miR-24-3p, miR-296-3p, miR-296-5p, miR-3131, miR-3162-5p, miR-3188, miR-3196, miR-3197, miR-320a, miR-342-5p, miR-3621, miR-3648, miR-3656, miR-365a-5p, miR-3665, miR-3679-5p, miR-371a-5p, miR-3940-5p, miR-423-5p, miR-4257, miR-4270, miR-4271, miR-4286, miR-4298, miR-4417, miR-4442, miR-4446-3p, miR-4448, miR-4454, miR-4467, miR-4472, miR-4507, miR-4516, miR-451a, miR-4649-5p, miR-4651, miR-4665-3p, miR-4674, miR-4675, miR-4689, miR-4695-5p, miR-4697-5p, miR-4725-3p, miR-4739, miR-4745-5p, miR-4763-3p, miR-4792, miR-486-3p, miR-5001-5p, miR-5195-3p, miR-550a-5p, miR-5698, miR-6075, miR-6088, miR-6089, miR-6125, miR-6126, miR-614, miR-615-5p, miR-619-5p, miR-638, miR-642b-3p, miR-650, miR-663a, miR-663b, miR-6717-5p, miR-6721-5p, miR-6726-5p, miR-6727-5p, miR-6738-5p, miR-6741-5p, miR-6749-5p, miR-6752-5p, miR-675-5p, miR-6757-5p, miR-6763-5p, miR-6765-5p, miR-6775-5p, miR-6780b-5p, miR-6782-5p, miR-6784-5p, miR-6800-5p, miR-6806-5p, miR-6840-3p, miR-6848-5p, miR-6851-5p, miR-6870-5p, miR-6872-3p, miR-6875-5p, miR-6877-5p, miR-6879-5p, miR-6880-5p, miR-6885-5p, miR-6887-5p, miR-7108-5p, miR-711, miR-7113-3p, miR-744-5p, miR-760, miR-7845-5p, miR-7847-3p, miR-7977, miR-8059, miR-8063, miR-8072, miR-874-3p, miR-92a-2-5p, miR-92b-5p, miR-940, miR-1228-3p, miR-1275, miR-1307-3p, miR-1343-5p, miR-23a-3p, miR-29b-3p, miR-3135b, miR-3185, miR-4532, miR-4690-5p, miR-4758-5p, miR-4783-3p, miR-6131, miR-625-3p, miR-6511a-5p, miR-6765-3p, miR-6816-5p, miR-6825-5p, miR-6845-5p, miR-7150, miR-7641, miR-7975, and miR-92a-3p, respectively), a congener thereof, a transcript thereof, or/and a variant or a derivative thereof. In this context, the gene, the congener, the transcript, the variant, and the derivative are as defined above.

(8) The target nucleic acid is preferably a human gene comprising a nucleotide sequence represented by any of SEQ ID NOs: 1 to 329 or a transcript thereof, more preferably the transcript, i.e., a miRNA or its precursor RNA, pri-miRNA or pre-miRNA, or a polynucleotide complementary thereto.

(9) The first target gene is the hsa-miR-6787-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(10) The second target gene is the hsa-miR-920 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(11) The third target gene is the hsa-miR-3622a-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(12) The fourth target gene is the hsa-miR-1185-1-3p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(13) The fifth target gene is the hsa-miR-4327 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(14) The sixth target gene is the hsa-miR-5739 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(15) The seventh target gene is the hsa-miR-937-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(16) The eighth target gene is the hsa-miR-1181 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(17) The ninth target gene is the hsa-miR-1185-2-3p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(18) The 10th target gene is the hsa-miR-1193 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(19) The 11th target gene is the hsa-miR-1207-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(20) The 12th target gene is the hsa-miR-1238-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(21) The 13th target gene is the hsa-miR-1246 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(22) The 14th target gene is the hsa-miR-1249-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(23) The 15th target gene is the hsa-miR-1292-3p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(24) The 16th target gene is the hsa-miR-1469 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(25) The 17th target gene is the hsa-miR-1470 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(26) The 18th target gene is the hsa-miR-197-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(27) The 19th target gene is the hsa-miR-208a-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(28) The 20th target gene is the hsa-miR-2110 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(29) The 21st target gene is the hsa-miR-211-3p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(30) The 22nd target gene is the hsa-miR-2467-3p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(31) The 23rd target gene is the hsa-miR-3122 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(32) The 24th target gene is the hsa-miR-3141 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(33) The 25th target gene is the hsa-miR-3156-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(34) The 26th target gene is the hsa-miR-3158-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(35) The 27th target gene is the hsa-miR-3160-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(36) The 28th target gene is the hsa-miR-3180-3p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(37) The 29th target gene is the hsa-miR-3191-3p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(38) The 30th target gene is the hsa-miR-3194-3p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(39) The 31st target gene is the hsa-miR-320b gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(40) The 32nd target gene is the hsa-miR-328-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(41) The 33rd target gene is the hsa-miR-3610 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(42) The 34th target gene is the hsa-miR-3619-3p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(43) The 35th target gene is the hsa-miR-3620-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(44) The 36th target gene is the hsa-miR-370-3p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(45) The 37th target gene is the hsa-miR-373-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(46) The 38th target gene is the hsa-miR-3917 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(47) The 39th target gene is the hsa-miR-3937 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(48) The 40th target gene is the hsa-miR-4259 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(49) The 41st target gene is the hsa-miR-4281 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(50) The 42nd target gene is the hsa-miR-4294 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(51) The 43rd target gene is the hsa-miR-4419b gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(52) The 44th target gene is the hsa-miR-4428 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(53) The 45th target gene is the hsa-miR-4429 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(54) The 46th target gene is the hsa-miR-4433a-3p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(55) The 47th target gene is the hsa-miR-4447 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(56) The 48th target gene is the hsa-miR-4449 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(57) The 49th target gene is the hsa-miR-4459 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(58) The 50th target gene is the hsa-miR-4480 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(59) The 51st target gene is the hsa-miR-4485-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(60) The 52nd target gene is the hsa-miR-4486 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(61) The 53rd target gene is the hsa-miR-4488 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(62) The 54th target gene is the hsa-miR-4489 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(63) The 55th target gene is the hsa-miR-4505 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(64) The 56th target gene is the hsa-miR-4513 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(65) The 57th target gene is the hsa-miR-4515 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(66) The 58th target gene is the hsa-miR-4530 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(67) The 59th target gene is the hsa-miR-4535 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(68) The 60th target gene is the hsa-miR-4635 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(69) The 61st target gene is the hsa-miR-4640-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(70) The 62nd target gene is the hsa-miR-4646-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(71) The 63rd target gene is the hsa-miR-4656 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(72) The 64th target gene is the hsa-miR-4663 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(73) The 65th target gene is the hsa-miR-4665-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(74) The 66th target gene is the hsa-miR-4706 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(75) The 67th target gene is the hsa-miR-4707-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(76) The 68th target gene is the hsa-miR-4708-3p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(77) The 69th target gene is the hsa-miR-4710 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(78) The 70th target gene is the hsa-miR-4718 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(79) The 71st target gene is the hsa-miR-4722-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(80) The 72nd target gene is the hsa-miR-4727-3p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(81) The 73rd target gene is the hsa-miR-4730 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(82) The 74th target gene is the hsa-miR-4734 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(83) The 75th target gene is the hsa-miR-4740-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(84) The 76th target gene is the hsa-miR-4747-3p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(85) The 77th target gene is the hsa-miR-4749-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(86) The 78th target gene is the hsa-miR-4755-3p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(87) The 79th target gene is the hsa-miR-4763-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(88) The 80th target gene is the hsa-miR-4787-3p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(89) The 81st target gene is the hsa-miR-5008-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(90) The 82nd target gene is the hsa-miR-5010-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(91) The 83rd target gene is the hsa-miR-504-3p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(92) The 84th target gene is the hsa-miR-5090 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(93) The 85th target gene is the hsa-miR-5100 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(94) The 86th target gene is the hsa-miR-5196-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(95) The 87th target gene is the hsa-miR-551b-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(96) The 88th target gene is the hsa-miR-557 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(97) The 89th target gene is the hsa-miR-5787 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(98) The 90th target gene is the hsa-miR-6090 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(99) The 91st target gene is the hsa-miR-6124 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(100) The 92nd target gene is the hsa-miR-6132 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(101) The 93rd target gene is the hsa-miR-6510-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(102) The 94th target gene is the hsa-miR-6511b-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(103) The 95th target gene is the hsa-miR-6515-3p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(104) The 96th target gene is the hsa-miR-654-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(105) The 97th target gene is the hsa-miR-658 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(106) The 98th target gene is the hsa-miR-668-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(107) The 99th target gene is the hsa-miR-6722-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(108) The 100th target gene is the hsa-miR-6724-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(109) The 101st target gene is the hsa-miR-6729-3p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(110) The 102nd target gene is the hsa-miR-6737-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(111) The 103rd target gene is the hsa-miR-6756-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(112) The 104th target gene is the hsa-miR-6762-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(113) The 105th target gene is the hsa-miR-6763-3p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(114) The 106th target gene is the hsa-miR-6766-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(115) The 107th target gene is the hsa-miR-6769a-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(116) The 108th target gene is the hsa-miR-6771-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(117) The 109th target gene is the hsa-miR-6786-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(118) The 110th target gene is the hsa-miR-6789-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(119) The 111th target gene is the hsa-miR-6794-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(120) The 112th target gene is the hsa-miR-6796-3p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(121) The 113th target gene is the hsa-miR-6797-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(122) The 114th target gene is the hsa-miR-6800-3p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(123) The 115th target gene is the hsa-miR-6802-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(124) The 116th target gene is the hsa-miR-6803-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(125) The 117th target gene is the hsa-miR-6805-3p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(126) The 118th target gene is the hsa-miR-6805-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(127) The 119th target gene is the hsa-miR-6807-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(128) The 120th target gene is the hsa-miR-6812-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(129) The 121st target gene is the hsa-miR-6819-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(130) The 122nd target gene is the hsa-miR-6822-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(131) The 123rd target gene is the hsa-miR-6824-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(132) The 124th target gene is the hsa-miR-6826-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(133) The 125th target gene is the hsa-miR-6850-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(134) The 126th target gene is the hsa-miR-6858-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(135) The 127th target gene is the hsa-miR-6861-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(136) The 128th target gene is the hsa-miR-6880-3p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(137) The 129th target gene is the hsa-miR-7107-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(138) The 130th target gene is the hsa-miR-7109-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(139) The 131st target gene is the hsa-miR-7114-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(140) The 132nd target gene is the hsa-miR-7704 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(141) The 133rd target gene is the hsa-miR-7846-3p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(142) The 134th target gene is the hsa-miR-8052 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(143) The 135th target gene is the hsa-miR-8060 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(144) The 136th target gene is the hsa-miR-8071 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(145) The 137th target gene is the hsa-miR-8073 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(146) The 138th target gene is the hsa-miR-874-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(147) The 139th target gene is the hsa-miR-204-3p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(148) The 140th target gene is the hsa-miR-3154 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(149) The 141st target gene is the hsa-miR-3960 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(150) The 142nd target gene is the hsa-miR-4433a-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(151) The 143rd target gene is the hsa-miR-4455 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(152) The 144th target gene is the hsa-miR-4462 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(153) The 145th target gene is the hsa-miR-4476 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(154) The 146th target gene is the hsa-miR-4508 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(155) The 147th target gene is the hsa-miR-4687-3p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(156) The 148th target gene is the hsa-miR-4687-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(157) The 149th target gene is the hsa-miR-4732-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(158) The 150th target gene is the hsa-miR-4771 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(159) The 151st target gene is the hsa-miR-642a-3p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(160) The 152nd target gene is the hsa-miR-6732-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(161) The 153rd target gene is the hsa-miR-6760-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(162) The 154th target gene is the hsa-miR-6799-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(163) The 155th target gene is the hsa-miR-6820-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(164) The 156th target gene is the hsa-miR-6821-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(165) The 157th target gene is the hsa-miR-6829-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(166) The 158th target gene is the hsa-miR-6893-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(167) The 159th target gene is the hsa-miR-7108-3p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(168) The 160th target gene is the hsa-miR-7111-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(169) The 161st target gene is the hsa-miR-8089 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(170) The 162nd target gene is the hsa-miR-885-3p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(171) The 163rd target gene is the hsa-miR-92b-3p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer.

(172) The 164th target gene is the hsa-miR-1343-3p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(173) The 165th target gene is the hsa-miR-6746-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(174) The 166th target gene is the hsa-miR-422a gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 2).

(175) The 167th target gene is the hsa-miR-187-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(176) The 168th target gene is the hsa-miR-4632-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(177) The 169th target gene is the hsa-miR-6791-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(178) The 170th target gene is the hsa-miR-103a-3p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 3).

(179) The 171st target gene is the hsa-miR-107 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 3).

(180) The 172nd target gene is the hsa-miR-1199-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(181) The 173rd target gene is the hsa-miR-1225-3p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(182) The 174th target gene is the hsa-miR-1225-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(183) The 175th target gene is the hsa-miR-1228-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(184) The 176th target gene is the hsa-miR-1229-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Non-Patent Literature 5).

(185) The 177th target gene is the hsa-miR-1233-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(186) The 178th target gene is the hsa-miR-1237-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(187) The 179th target gene is the hsa-miR-1247-3p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(188) The 180th target gene is the hsa-miR-1249-3p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 5).

(189) The 181st target gene is the hsa-miR-1254 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Non-Patent Literature 6).

(190) The 182nd target gene is the hsa-miR-1260b gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(191) The 183rd target gene is the hsa-miR-1268a gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(192) The 184th target gene is the hsa-miR-1268b gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(193) The 185th target gene is the hsa-miR-1273g-3p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(194) The 186th target gene is the hsa-miR-128-1-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(195) The 187th target gene is the hsa-miR-128-2-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(196) The 188th target gene is the hsa-miR-1290 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Non-Patent Literature 1).

(197) The 189th target gene is the hsa-miR-150-3p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 3).

(198) The 190th target gene is the hsa-miR-17-3p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(199) The 191st target gene is the hsa-miR-1908-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(200) The 192nd target gene is the hsa-miR-1909-3p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 4).

(201) The 193rd target gene is the hsa-miR-1914-3p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(202) The 194th target gene is the hsa-miR-1915-3p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(203) The 195th target gene is the hsa-miR-191-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(204) The 196th target gene is the hsa-miR-22-3p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(205) The 197th target gene is the hsa-miR-23b-3p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 4).

(206) The 198th target gene is the hsa-miR-24-3p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 2).

(207) The 199th target gene is the hsa-miR-296-3p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(208) The 200th target gene is the hsa-miR-296-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 2).

(209) The 201st target gene is the hsa-miR-3131 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(210) The 202nd target gene is the hsa-miR-3162-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(211) The 203rd target gene is the hsa-miR-3188 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(212) The 204th target gene is the hsa-miR-3196 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(213) The 205th target gene is the hsa-miR-3197 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(214) The 206th target gene is the hsa-miR-320a gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 2).

(215) The 207th target gene is the hsa-miR-342-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Non-Patent Literature 3).

(216) The 208th target gene is the hsa-miR-3621 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(217) The 209th target gene is the hsa-miR-3648 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(218) The 210th target gene is the hsa-miR-3656 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(219) The 211th target gene is the hsa-miR-365a-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(220) The 212th target gene is the hsa-miR-3665 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(221) The 213th target gene is the hsa-miR-3679-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(222) The 214th target gene is the hsa-miR-371a-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(223) The 215th target gene is the hsa-miR-3940-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(224) The 216th target gene is the hsa-miR-423-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 4).

(225) The 217th target gene is the hsa-miR-4257 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(226) The 218th target gene is the hsa-miR-4270 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(227) The 219th target gene is the hsa-miR-4271 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(228) The 220th target gene is the hsa-miR-4286 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(229) The 221st target gene is the hsa-miR-4298 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(230) The 222nd target gene is the hsa-miR-4417 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(231) The 223rd target gene is the hsa-miR-4442 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(232) The 224th target gene is the hsa-miR-4446-3p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(233) The 225th target gene is the hsa-miR-4448 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(234) The 226th target gene is the hsa-miR-4454 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(235) The 227th target gene is the hsa-miR-4467 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(236) The 228th target gene is the hsa-miR-4472 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(237) The 229th target gene is the hsa-miR-4507 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(238) The 230th target gene is the hsa-miR-4516 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(239) The 231st target gene is the hsa-miR-451a gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(240) The 232nd target gene is the hsa-miR-4649-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(241) The 233rd target gene is the hsa-miR-4651 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(242) The 234th target gene is the hsa-miR-4665-3p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(243) The 235th target gene is the hsa-miR-4674 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(244) The 236th target gene is the hsa-miR-4675 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(245) The 237th target gene is the hsa-miR-4689 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(246) The 238th target gene is the hsa-miR-4695-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(247) The 239th target gene is the hsa-miR-4697-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(248) The 240th target gene is the hsa-miR-4725-3p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(249) The 241st target gene is the hsa-miR-4739 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(250) The 242nd target gene is the hsa-miR-4745-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(251) The 243rd target gene is the hsa-miR-4763-3p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(252) The 244th target gene is the hsa-miR-4792 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(253) The 245th target gene is the hsa-miR-486-3p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(254) The 246th target gene is the hsa-miR-5001-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(255) The 247th target gene is the hsa-miR-5195-3p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(256) The 248th target gene is the hsa-miR-550a-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Non-Patent Literature 4).

(257) The 249th target gene is the hsa-miR-5698 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(258) The 250th target gene is the hsa-miR-6075 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(259) The 251st target gene is the hsa-miR-6088 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(260) The 252nd target gene is the hsa-miR-6089 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(261) The 253rd target gene is the hsa-miR-6125 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(262) The 254th target gene is the hsa-miR-6126 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(263) The 255th target gene is the hsa-miR-614 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(264) The 256th target gene is the hsa-miR-615-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(265) The 257th target gene is the hsa-miR-619-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(266) The 258th target gene is the hsa-miR-638 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 2).

(267) The 259th target gene is the hsa-miR-642b-3p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(268) The 260th target gene is the hsa-miR-650 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Non-Patent Literature 2).

(269) The 261st target gene is the hsa-miR-663a gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(270) The 262nd target gene is the hsa-miR-663b gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(271) The 263rd target gene is the hsa-miR-6717-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(272) The 264th target gene is the hsa-miR-6721-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(273) The 265th target gene is the hsa-miR-6726-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(274) The 266th target gene is the hsa-miR-6727-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(275) The 267th target gene is the hsa-miR-6738-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(276) The 268th target gene is the hsa-miR-6741-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(277) The 269th target gene is the hsa-miR-6749-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(278) The 270th target gene is the hsa-miR-6752-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(279) The 271st target gene is the hsa-miR-675-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(280) The 272nd target gene is the hsa-miR-6757-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(281) The 273rd target gene is the hsa-miR-6763-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(282) The 274th target gene is the hsa-miR-6765-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(283) The 275th target gene is the hsa-miR-6775-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(284) The 276th target gene is the hsa-miR-6780b-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(285) The 277th target gene is the hsa-miR-6782-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(286) The 278th target gene is the hsa-miR-6784-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(287) The 279th target gene is the hsa-miR-6800-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(288) The 280th target gene is the hsa-miR-6806-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(289) The 281st target gene is the hsa-miR-6840-3p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(290) The 282nd target gene is the hsa-miR-6848-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(291) The 283rd target gene is the hsa-miR-6851-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(292) The 284th target gene is the hsa-miR-6870-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(293) The 285th target gene is the hsa-miR-6872-3p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(294) The 286th target gene is the hsa-miR-6875-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(295) The 287th target gene is the hsa-miR-6877-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(296) The 288th target gene is the hsa-miR-6879-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(297) The 289th target gene is the hsa-miR-6880-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(298) The 290th target gene is the hsa-miR-6885-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(299) The 291st target gene is the hsa-miR-6887-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(300) The 292nd target gene is the hsa-miR-7108-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(301) The 293rd target gene is the hsa-miR-711 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(302) The 294th target gene is the hsa-miR-7113-3p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(303) The 295th target gene is the hsa-miR-744-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 5).

(304) The 296th target gene is the hsa-miR-760 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(305) The 297th target gene is the hsa-miR-7845-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(306) The 298th target gene is the hsa-miR-7847-3p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(307) The 299th target gene is the hsa-miR-7977 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(308) The 300th target gene is the hsa-miR-8059 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(309) The 301st target gene is the hsa-miR-8063 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(310) The 302nd target gene is the hsa-miR-8072 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(311) The 303rd target gene is the hsa-miR-874-3p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 5).

(312) The 304th target gene is the hsa-miR-92a-2-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(313) The 305th target gene is the hsa-miR-92b-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(314) The 306th target gene is the hsa-miR-940 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(315) The 307th target gene is the hsa-miR-1228-3p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(316) The 308th target gene is the hsa-miR-1275 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 5).

(317) The 309th target gene is the hsa-miR-1307-3p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(318) The 310th target gene is the hsa-miR-1343-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(319) The 311th target gene is the hsa-miR-23a-3p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 2).

(320) The 312th target gene is the hsa-miR-29b-3p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 2).

(321) The 313th target gene is the hsa-miR-3135b gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(322) The 314th target gene is the hsa-miR-3185 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(323) The 315th target gene is the hsa-miR-4532 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(324) The 316th target gene is the hsa-miR-4690-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(325) The 317th target gene is the hsa-miR-4758-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(326) The 318th target gene is the hsa-miR-4783-3p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(327) The 319th target gene is the hsa-miR-6131 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(328) The 320th target gene is the hsa-miR-625-3p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 4).

(329) The 321st target gene is the hsa-miR-65111a-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(330) The 322nd target gene is the hsa-miR-6765-3p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(331) The 323rd target gene is the hsa-miR-6816-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(332) The 324th target gene is the hsa-miR-6825-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(333) The 325th target gene is the hsa-miR-6845-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(334) The 326th target gene is the hsa-miR-7150 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(335) The 327th target gene is the hsa-miR-7641 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(336) The 328th target gene is the hsa-miR-7975 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(337) The 329th target gene is the hsa-miR-92a-3p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for lung cancer (Patent Literature 1).

(338) In one aspect, the present invention relates to a marker containing at least one of the target nucleic acids described above for detecting lung cancer or for diagnosing lung cancer.

(339) In one aspect, the present invention relates to use of at least one of the target nucleic acids described above for detecting lung cancer or for diagnosing lung cancer.

(340) 2. Nucleic Acid for Detection of Lung Cancer

(341) In the present invention, the nucleic acids for detecting lung cancer, e.g., nucleic acid probes or primers that can be used for diagnosing lung cancer enable qualitative and/or quantitative measurement of the presence, expression levels, or existing amounts (abundance) of: human-derived miR-6787-5p, miR-920, miR-3622a-5p, miR-1185-1-3p, miR-4327, miR-5739, miR-937-5p, miR-1181, miR-1185-2-3p, miR-1193, miR-1207-5p, miR-1238-5p, miR-1246, miR-1249-5p, miR-1292-3p, miR-1469, miR-1470, miR-197-5p, miR-208a-5p, miR-2110, miR-211-3p, miR-2467-3p, miR-3122, miR-3141, miR-3156-5p, miR-3158-5p, miR-3160-5p, miR-3180-3p, miR-3191-3p, miR-3194-3p, miR-320b, miR-328-5p, miR-3610, miR-3619-3p, miR-3620-5p, miR-370-3p, miR-373-5p, miR-3917, miR-3937, miR-4259, miR-4281, miR-4294, miR-4419b, miR-4428, miR-4429, miR-4433a-3p, miR-4447, miR-4449, miR-4459, miR-4480, miR-4485-5p, miR-4486, miR-4488, miR-4489, miR-4505, miR-4513, miR-4515, miR-4530, miR-4535, miR-4635, miR-4640-5p, miR-4646-5p, miR-4656, miR-4663, miR-4665-5p, miR-4706, miR-4707-5p, miR-4708-3p, miR-4710, miR-4718, miR-4722-5p, miR-4727-3p, miR-4730, miR-4734, miR-4740-5p, miR-4747-3p, miR-4749-5p, miR-4755-3p, miR-4763-5p, miR-4787-3p, miR-5008-5p, miR-5010-5p, miR-504-3p, miR-5090, miR-5100, miR-5196-5p, miR-551b-5p, miR-557, miR-5787, miR-6090, miR-6124, miR-6132, miR-6510-5p, miR-6511b-5p, miR-6515-3p, miR-654-5p, miR-658, miR-668-5p, miR-6722-5p, miR-6724-5p, miR-6729-3p, miR-6737-5p, miR-6756-5p, miR-6762-5p, miR-6763-3p, miR-6766-5p, miR-6769a-5p, miR-6771-5p, miR-6786-5p, miR-6789-5p, miR-6794-5p, miR-6796-3p, miR-6797-5p, miR-6800-3p, miR-6802-5p, miR-6803-5p, miR-6805-3p, miR-6805-5p, miR-6807-5p, miR-6812-5p, miR-6819-5p, miR-6822-5p, miR-6824-5p, miR-6826-5p, miR-6850-5p, miR-6858-5p, miR-6861-5p, miR-6880-3p, miR-7107-5p, miR-7109-5p, miR-7114-5p, miR-7704, miR-7846-3p, miR-8052, miR-8060, miR-8071, miR-8073, miR-874-5p, miR-204-3p, miR-3154, miR-3960, miR-4433a-5p, miR-4455, miR-4462, miR-4476, miR-4508, miR-4687-3p, miR-4687-5p, miR-4732-5p, miR-4771, miR-642a-3p, miR-6732-5p, miR-6760-5p, miR-6799-5p, miR-6820-5p, miR-6821-5p, miR-6829-5p, miR-6893-5p, miR-7108-3p, miR-7111-5p, miR-8089, miR-885-3p, miR-92b-3p, miR-1343-3p, miR-6746-5p, miR-422a, miR-187-5p, miR-4632-5p, miR-6791-5p, miR-103a-3p, miR-107, miR-1199-5p, miR-1225-3p, miR-1225-5p, miR-1228-5p, miR-1229-5p, miR-1233-5p, miR-1237-5p, miR-1247-3p, miR-1249-3p, miR-1254, miR-1260b, miR-1268a, miR-1268b, miR-1273g-3p, miR-128-1-5p, miR-128-2-5p, miR-1290, miR-150-3p, miR-17-3p, miR-1908-5p, miR-1909-3p, miR-1914-3p, miR-1915-3p, miR-1191-5p, miR-22-3p, miR-23b-3p, miR-24-3p, miR-296-3p, miR-296-5p, miR-3131, miR-3162-5p, miR-3188, miR-3196, miR-3197, miR-320a, miR-342-5p, miR-3621, miR-3648, miR-3656, miR-365a-5p, miR-3665, miR-3679-5p, miR-371a-5p, miR-3940-5p, miR-423-5p, miR-4257, miR-4270, miR-4271, miR-4286, miR-4298, miR-4417, miR-4442, miR-4446-3p, miR-4448, miR-4454, miR-4467, miR-4472, miR-4507, miR-4516, miR-451a, miR-4649-5p, miR-4651, miR-4665-3p, miR-4674, miR-4675, miR-4689, miR-4695-5p, miR-4697-5p, miR-4725-3p, miR-4739, miR-4745-5p, miR-4763-3p, miR-4792, miR-486-3p, miR-5001-5p, miR-5195-3p, miR-550a-5p, miR-5698, miR-6075, miR-6088, miR-6089, miR-6125, miR-6126, miR-614, miR-615-5p, miR-619-5p, miR-638, miR-642b-3p, miR-650, miR-663a, miR-663b, miR-6717-5p, miR-6721-5p, miR-6726-5p, miR-6727-5p, miR-6738-5p, miR-6741-5p, miR-6749-5p, miR-6752-5p, miR-675-5p, miR-6757-5p, miR-6763-5p, miR-6765-5p, miR-6775-5p, miR-6780b-5p, miR-6782-5p, miR-6784-5p, miR-6800-5p, miR-6806-5p, miR-6840-3p, miR-6848-5p, miR-6851-5p, miR-6870-5p, miR-6872-3p, miR-6875-5p, miR-6877-5p, miR-6879-5p, miR-6880-5p, miR-6885-5p, miR-6887-5p, miR-7108-5p, miR-711, miR-7113-3p, miR-744-5p, miR-760, miR-7845-5p, miR-7847-3p, miR-7977, miR-8059, miR-8063, miR-8072, miR-874-3p, miR-92a-2-5p, miR-92b-5p, miR-940, miR-1228-3p, miR-1275, miR-1307-3p, miR-1343-5p, miR-23a-3p, miR-29b-3p, miR-3135b, miR-3185, miR-4532, miR-4690-5p, miR-4758-5p, miR-4783-3p, miR-6131, miR-625-3p, miR-6511a-5p, miR-6765-3p, miR-6816-5p, miR-6825-5p, miR-6845-5p, miR-7150, miR-7641, miR-7975, and miR-92a-3p, as target nucleic acids for lung cancer, or combinations thereof, congeners thereof, transcripts thereof, or variants or derivatives thereof.

(342) The expression levels of the target nucleic acids described above are increased or decreased (hereinafter, referred to as “increased/decreased”) depending on the types of the target nucleic acids in subjects having lung cancer as compared with healthy subjects, benign bone and soft tissue tumor patients and benign breast disease patients, and subjects having a cancer other than lung cancer. Hence, the kit or device of the present invention can be effectively used for measuring expression levels of the target nucleic acids in body fluids from subjects (e.g., humans) suspected of having lung cancer and body fluids from healthy subjects, benign bone and soft tissue tumor patients and benign breast disease patients (or diseased animals), and patients (or cancer animals) having a cancer other than lung cancer, and thereby detecting lung cancer through the comparison thereof.

(343) The nucleic acid probe or primer(s) that can be used in the present invention is, for example, a nucleic acid probe capable of specifically binding to a polynucleotide consisting of a nucleotide sequence represented by at least one of SEQ ID NOs: 1 to 163; or a primer(s) for amplifying a polynucleotide consisting of a nucleotide sequence represented by at least one of SEQ ID NOs: 1 to 163.

(344) The nucleic acid probe or primer(s) that can be used in the present invention may further comprise, for example, a nucleic acid probe capable of specifically binding to a polynucleotide consisting of a nucleotide sequence represented by at least one of SEQ ID NOs: 164 to 329; or a primer(s) for amplifying a polynucleotide consisting of a nucleotide sequence represented by at least one of SEQ ID NOs: 164 to 329.

(345) In a preferred embodiment of the present invention, specifically, these nucleic acid probes or primers comprise a combination of one or more polynucleotides selected from: a group of polynucleotides comprising nucleotide sequences represented by any of SEQ ID NOs: 1 to 1000, or the nucleotide sequences in which the nucleic acid u is replaced with t, and a group of complementary polynucleotides thereof; a group of polynucleotides respectively hybridizing under stringent conditions (mentioned later) to DNAs consisting of nucleotide sequences complementary to these nucleotide sequences, and a group of complementary polynucleotides thereof; and a group of polynucleotides comprising 15 or more, preferably 17 or more consecutive nucleotides and being from the nucleotide sequences of these polynucleotide groups. These polynucleotides can be used as nucleic acid probes and primers for detecting the lung cancer markers as target nucleic acids.

(346) More specifically, examples of the nucleic acid probes or the primers that can be used in the present invention include one or more polynucleotides selected from the group consisting of the following polynucleotides (a) to (e):

(347) (a) a polynucleotide consisting of a nucleotide sequence represented by any of SEQ ID NOs: 1 to 163 or a nucleotide sequence derived from the nucleotide sequence in which the nucleic acid u is replaced with t, a variant thereof, a derivative thereof, or a fragment thereof comprising 15 or more consecutive nucleotides;
(b) a polynucleotide comprising a nucleotide sequence represented by any of SEQ ID NOs: 1 to 163;
(c) a polynucleotide consisting of a nucleotide sequence complementary to a nucleotide sequence represented by any of SEQ ID NOs: 1 to 163, or a nucleotide sequence derived from the nucleotide sequence in which the nucleic acid u is replaced with t, a variant thereof, a derivative thereof, or a fragment thereof comprising 15 or more consecutive nucleotides;
(d) a polynucleotide comprising a nucleotide sequence complementary to a nucleotide sequence represented by any of SEQ ID NOs: 1 to 163, or a nucleotide sequence derived from the nucleotide sequence in which the nucleic acid u is replaced with t; and
(e) a polynucleotide hybridizing under stringent conditions to any of the polynucleotides (a) to (d).

(348) In addition to at least one polynucleotide selected from any of the polynucleotides (a) to (e), the nucleic acid probes or the primers that can be used in the present invention may further comprise any of the following polynucleotides (f) to (j):

(349) (f) a polynucleotide consisting of a nucleotide sequence represented by any of SEQ ID NOs: 164 to 329, or a nucleotide sequence derived from the nucleotide sequence in which the nucleic acid u is replaced with t, a variant thereof, a derivative thereof, or a fragment thereof comprising 15 or more consecutive nucleotides;
(g) a polynucleotide comprising a nucleotide sequence represented by any of SEQ ID NOs: 164 to 329;
(h) a polynucleotide consisting of a nucleotide sequence complementary to a nucleotide sequence represented by any of SEQ ID NOs: 164 to 329, or a nucleotide sequence derived from the nucleotide sequence in which the nucleic acid u is replaced with t, a variant thereof, a derivative thereof, or a fragment thereof comprising 15 or more consecutive nucleotides;
(i) a polynucleotide comprising a nucleotide sequence complementary to a nucleotide sequence represented by any of SEQ ID NOs: 164 to 329, or a nucleotide sequence derived from the nucleotide sequence in which the nucleic acid u is replaced with t; and
(j) a polynucleotide hybridizing under stringent conditions to any of the polynucleotides (f) to (i).

(350) These polynucleotides or fragments thereof used in the present invention may each be DNA or may each be RNA.

(351) The polynucleotides that can be used in the present invention can be prepared by use of a general technique such as a DNA recombination technique, a PCR method, or a method using an automatic DNA/RNA synthesizer.

(352) The DNA recombination technique and the PCR method may employ techniques described in, for example, Ausubel et al., Current Protocols in Molecular Biology, John Willey & Sons, US (1993); and Sambrook et al., Molecular Cloning—A Laboratory Manual, Cold Spring Harbor Laboratory Press, US (1989).

(353) The human-derived miR-6787-5p, miR-920, miR-3622a-5p, miR-1185-1-3p, miR-4327, miR-5739, miR-937-5p, miR-1181, miR-1185-2-3p, miR-1193, miR-1207-5p, miR-1238-5p, miR-1246, miR-1249-5p, miR-1292-3p, miR-1469, miR-1470, miR-197-5p, miR-208a-5p, miR-2110, miR-211-3p, miR-2467-3p, miR-3122, miR-3141, miR-3156-5p, miR-3158-5p, miR-3160-5p, miR-3180-3p, miR-3191-3p, miR-3194-3p, miR-320b, miR-328-5p, miR-3610, miR-3619-3p, miR-3620-5p, miR-370-3p, miR-373-5p, miR-3917, miR-3937, miR-4259, miR-4281, miR-4294, miR-4419b, miR-4428, miR-4429, miR-4433a-3p, miR-4447, miR-4449, miR-4459, miR-4480, miR-4485-5p, miR-4486, miR-4488, miR-4489, miR-4505, miR-4513, miR-4515, miR-4530, miR-4535, miR-4635, miR-4640-5p, miR-4646-5p, miR-4656, miR-4663, miR-4665-5p, miR-4706, miR-4707-5p, miR-4708-3p, miR-4710, miR-4718, miR-4722-5p, miR-4727-3p, miR-4730, miR-4734, miR-4740-5p, miR-4747-3p, miR-4749-5p, miR-4755-3p, miR-4763-5p, miR-4787-3p, miR-5008-5p, miR-5010-5p, miR-504-3p, miR-5090, miR-5100, miR-5196-5p, miR-551b-5p, miR-557, miR-5787, miR-6090, miR-6124, miR-6132, miR-6510-5p, miR-6511b-5p, miR-6515-3p, miR-654-5p, miR-658, miR-668-5p, miR-6722-5p, miR-6724-5p, miR-6729-3p, miR-6737-5p, miR-6756-5p, miR-6762-5p, miR-6763-3p, miR-6766-5p, miR-6769a-5p, miR-6771-5p, miR-6786-5p, miR-6789-5p, miR-6794-5p, miR-6796-3p, miR-6797-5p, miR-6800-3p, miR-6802-5p, miR-6803-5p, miR-6805-3p, miR-6805-5p, miR-6807-5p, miR-6812-5p, miR-6819-5p, miR-6822-5p, miR-6824-5p, miR-6826-5p, miR-6850-5p, miR-6858-5p, miR-6861-5p, miR-6880-3p, miR-7107-5p, miR-7109-5p, miR-7114-5p, miR-7704, miR-7846-3p, miR-8052, miR-8060, miR-8071, miR-8073, miR-874-5p, miR-204-3p, miR-3154, miR-3960, miR-4433a-5p, miR-4455, miR-4462, miR-4476, miR-4508, miR-4687-3p, miR-4687-5p, miR-4732-5p, miR-4771, miR-642a-3p, miR-6732-5p, miR-6760-5p, miR-6799-5p, miR-6820-5p, miR-6821-5p, miR-6829-5p, miR-6893-5p, miR-7108-3p, miR-7111-5p, miR-8089, miR-885-3p, miR-92b-3p, miR-1343-3p, miR-6746-5p, miR-422a, miR-187-5p, miR-4632-5p, miR-6791-5p, miR-103a-3p, miR-107, miR-1199-5p, miR-1225-3p, miR-1225-5p, miR-1228-5p, miR-1229-5p, miR-1233-5p, miR-1237-5p, miR-1247-3p, miR-1249-3p, miR-1254, miR-1260b, miR-1268a, miR-1268b, miR-1273g-3p, miR-128-1-5p, miR-128-2-5p, miR-1290, miR-150-3p, miR-17-3p, miR-1908-5p, miR-1909-3p, miR-1914-3p, miR-1915-3p, miR-191-5p, miR-22-3p, miR-23b-3p, miR-24-3p, miR-296-3p, miR-296-5p, miR-3131, miR-3162-5p, miR-3188, miR-3196, miR-3197, miR-320a, miR-342-5p, miR-3621, miR-3648, miR-3656, miR-365a-5p, miR-3665, miR-3679-5p, miR-371a-5p, miR-3940-5p, miR-423-5p, miR-4257, miR-4270, miR-4271, miR-4286, miR-4298, miR-4417, miR-4442, miR-4446-3p, miR-4448, miR-4454, miR-4467, miR-4472, miR-4507, miR-4516, miR-451a, miR-4649-5p, miR-4651, miR-4665-3p, miR-4674, miR-4675, miR-4689, miR-4695-5p, miR-4697-5p, miR-4725-3p, miR-4739, miR-4745-5p, miR-4763-3p, miR-4792, miR-486-3p, miR-5001-5p, miR-5195-3p, miR-550a-5p, miR-5698, miR-6075, miR-6088, miR-6089, miR-6125, miR-6126, miR-614, miR-615-5p, miR-619-5p, miR-638, miR-642b-3p, miR-650, miR-663a, miR-663b, miR-6717-5p, miR-6721-5p, miR-6726-5p, miR-6727-5p, miR-6738-5p, miR-6741-5p, miR-6749-5p, miR-6752-5p, miR-675-5p, miR-6757-5p, miR-6763-5p, miR-6765-5p, miR-6775-5p, miR-6780b-5p, miR-6782-5p, miR-6784-5p, miR-6800-5p, miR-6806-5p, miR-6840-3p, miR-6848-5p, miR-6851-5p, miR-6870-5p, miR-6872-3p, miR-6875-5p, miR-6877-5p, miR-6879-5p, miR-6880-5p, miR-6885-5p, miR-6887-5p, miR-7108-5p, miR-711, miR-7113-3p, miR-744-5p, miR-760, miR-7845-5p, miR-7847-3p, miR-7977, miR-8059, miR-8063, miR-8072, miR-874-3p, miR-92a-2-5p, miR-92b-5p, miR-940, miR-1228-3p, miR-1275, miR-1307-3p, miR-1343-5p, miR-23a-3p, miR-29b-3p, miR-3135b, miR-3185, miR-4532, miR-4690-5p, miR-4758-5p, miR-4783-3p, miR-6131, miR-625-3p, miR-6511a-5p, miR-6765-3p, miR-6816-5p, miR-6825-5p, miR-6845-5p, miR-7150, miR-7641, miR-7975, and miR-92a-3p represented by SEQ ID NOs: 1 to 329 are known, and methods to obtain them are also known as mentioned above. Therefore, each polynucleotide that can be used as a nucleic acid probe or a primer in the present invention can be prepared by cloning the gene.

(354) Such nucleic acid probes or primers can be chemically synthesized using an automatic DNA synthesizer. In general, the phosphoramidite method is used in this synthesis, and single-stranded DNA in length of up to approximately 100 nucleotides can be automatically synthesized by this method. The automatic DNA synthesizer is commercially available from, for example, Polygen GmbH, ABI, or Applied Biosystems, Inc.

(355) Alternatively, the polynucleotides of the present invention can also be prepared by cDNA cloning methods. The cDNA cloning technique may employ, for example, microRNA Cloning Kit Wako.

(356) In this context, the sequences of the nucleic acid probes and the primers for detecting the polynucleotide consisting of a nucleotide sequence represented by any of SEQ ID NOs: 1 to 329 do not exist as miRNAs or precursors thereof in the living body or in vivo. For example, the nucleotide sequences represented by SEQ ID NO: 142 and SEQ ID NO: 46 are produced from the precursor represented by SEQ ID NO: 382. This precursor has a hairpin-like structure as shown in FIG. 1, and the nucleotide sequences represented by SEQ ID NO: 142 and SEQ ID NO: 46 have mismatch sequences with each other. As such, a nucleotide sequence completely complementary to the nucleotide sequence represented by SEQ ID NO: 142 or SEQ ID NO: 46 does not naturally occur in vivo. Therefore, the nucleic acid probes and the primers for detecting the nucleotide sequence represented by any of SEQ ID NOs: 1 to 329 can have artificial nucleotide sequences that do not exist in the living body or in vivo.

(357) 3. Kit or Device for Detection of Lung Cancer

(358) The present invention also provides a kit or a device for detecting lung cancer, comprising one or more polynucleotides (which may include a variant, a fragment, or a derivative thereof) that can be used as nucleic acid probes or primers in the present invention for measuring target nucleic acids as lung cancer markers.

(359) The target nucleic acids as lung cancer markers according to the present invention are preferably selected from the following group A:

(360) Group A:

(361) miR-6787-5p, miR-920, miR-3622a-5p, miR-1185-1-3p, miR-4327, miR-5739, miR-937-5p, miR-1181, miR-1185-2-3p, miR-1193, miR-1207-5p, miR-1238-5p, miR-1246, miR-1249-5p, miR-1292-3p, miR-1469, miR-1470, miR-197-5p, miR-208a-5p, miR-2110, miR-211-3p, miR-2467-3p, miR-3122, miR-3141, miR-3156-5p, miR-3158-5p, miR-3160-5p, miR-3180-3p, miR-3191-3p, miR-3194-3p, miR-320b, miR-328-5p, miR-3610, miR-3619-3p, miR-3620-5p, miR-370-3p, miR-373-5p, miR-3917, miR-3937, miR-4259, miR-4281, miR-4294, miR-4419b, miR-4428, miR-4429, miR-4433a-3p, miR-4447, miR-4449, miR-4459, miR-4480, miR-4485-5p, miR-4486, miR-4488, miR-4489, miR-4505, miR-4513, miR-4515, miR-4530, miR-4535, miR-4635, miR-4640-5p, miR-4646-5p, miR-4656, miR-4663, miR-4665-5p, miR-4706, miR-4707-5p, miR-4708-3p, miR-4710, miR-4718, miR-4722-5p, miR-4727-3p, miR-4730, miR-4734, miR-4740-5p, miR-4747-3p, miR-4749-5p, miR-4755-3p, miR-4763-5p, miR-4787-3p, miR-5008-5p, miR-5010-5p, miR-504-3p, miR-5090, miR-5100, miR-5196-5p, miR-551b-5p, miR-557, miR-5787, miR-6090, miR-6124, miR-6132, miR-6510-5p, miR-6511b-5p, miR-6515-3p, miR-654-5p, miR-658, miR-668-5p, miR-6722-5p, miR-6724-5p, miR-6729-3p, miR-6737-5p, miR-6756-5p, miR-6762-5p, miR-6763-3p, miR-6766-5p, miR-6769a-5p, miR-6771-5p, miR-6786-5p, miR-6789-5p, miR-6794-5p, miR-6796-3p, miR-6797-5p, miR-6800-3p, miR-6802-5p, miR-6803-5p, miR-6805-3p, miR-6805-5p, miR-6807-5p, miR-6812-5p, miR-6819-5p, miR-6822-5p, miR-6824-5p, miR-6826-5p, miR-6850-5p, miR-6858-5p, miR-6861-5p, miR-6880-3p, miR-7107-5p, miR-7109-5p, miR-7114-5p, miR-7704, miR-7846-3p, miR-8052, miR-8060, miR-8071, miR-8073, miR-874-5p, miR-204-3p, miR-3154, miR-3960, miR-4433a-5p, miR-4455, miR-4462, miR-4476, miR-4508, miR-4687-3p, miR-4687-5p, miR-4732-5p, miR-4771, miR-642a-3p, miR-6732-5p, miR-6760-5p, miR-6799-5p, miR-6820-5p, miR-6821-5p, miR-6829-5p, miR-6893-5p, miR-7108-3p, miR-7111-5p, miR-8089, miR-885-3p, and miR-92b-3p.

(362) Additional target nucleic acids that may be optionally used in the measurement are preferably selected from the following group B:

(363) Group B:

(364) miR-1343-3p, miR-6746-5p, miR-422a, miR-187-5p, miR-4632-5p, miR-6791-5p, miR-103a-3p, miR-107, miR-1199-5p, miR-1225-3p, miR-1225-5p, miR-1228-5p, miR-1229-5p, miR-1233-5p, miR-1237-5p, miR-1247-3p, miR-1249-3p, miR-1254, miR-1260b, miR-1268a, miR-1268b, miR-1273g-3p, miR-128-1-5p, miR-128-2-5p, miR-1290, miR-150-3p, miR-17-3p, miR-1908-5p, miR-1909-3p, miR-1914-3p, miR-1915-3p, miR-191-5p, miR-22-3p, miR-23b-3p, miR-24-3p, miR-296-3p, miR-296-5p, miR-3131, miR-3162-5p, miR-3188, miR-3196, miR-3197, miR-320a, miR-342-5p, miR-3621, miR-3648, miR-3656, miR-365a-5p, miR-3665, miR-3679-5p, miR-371a-5p, miR-3940-5p, miR-423-5p, miR-4257, miR-4270, miR-4271, miR-4286, miR-4298, miR-4417, miR-4442, miR-4446-3p, miR-4448, miR-4454, miR-4467, miR-4472, miR-4507, miR-4516, miR-451a, miR-4649-5p, miR-4651, miR-4665-3p, miR-4674, miR-4675, miR-4689, miR-4695-5p, miR-4697-5p, miR-4725-3p, miR-4739, miR-4745-5p, miR-4763-3p, miR-4792, miR-486-3p, miR-5001-5p, miR-5195-3p, miR-550a-5p, miR-5698, miR-6075, miR-6088, miR-6089, miR-6125, miR-6126, miR-614, miR-615-5p, miR-619-5p, miR-638, miR-642b-3p, miR-650, miR-663a, miR-663b, miR-6717-5p, miR-6721-5p, miR-6726-5p, miR-6727-5p, miR-6738-5p, miR-6741-5p, miR-6749-5p, miR-6752-5p, miR-675-5p, miR-6757-5p, miR-6763-5p, miR-6765-5p, miR-6775-5p, miR-6780b-5p, miR-6782-5p, miR-6784-5p, miR-6800-5p, miR-6806-5p, miR-6840-3p, miR-6848-5p, miR-6851-5p, miR-6870-5p, miR-6872-3p, miR-6875-5p, miR-6877-5p, miR-6879-5p, miR-6880-5p, miR-6885-5p, miR-6887-5p, miR-7108-5p, miR-711, miR-7113-3p, miR-744-5p, miR-760, miR-7845-5p, miR-7847-3p, miR-7977, miR-8059, miR-8063, miR-8072, miR-874-3p, miR-92a-2-5p, miR-92b-5p, miR-940, miR-1228-3p, miR-1275, miR-1307-3p, miR-1343-5p, miR-23a-3p, miR-29b-3p, miR-3135b, miR-3185, miR-4532, miR-4690-5p, miR-4758-5p, miR-4783-3p, miR-6131, miR-625-3p, miR-6511a-5p, miR-6765-3p, miR-6816-5p, miR-6825-5p, miR-6845-5p, miR-7150, miR-7641, miR-7975, and miR-92a-3p.

(365) The kit or the device of the present invention comprises one or more nucleic acids capable of specifically binding to any of the target nucleic acids as the lung cancer markers described above or nucleic acids for detecting the target nucleic acids, preferably one or more polynucleotides selected from the polynucleotides described in the preceding Section 2, or variants thereof.

(366) Specifically, the kit or the device of the present invention can comprise at least one polynucleotide comprising (or consisting of), for example, a nucleotide sequence represented by any of SEQ ID NOs: 1 to 163, or a nucleotide sequence derived from the nucleotide sequence in which the nucleic acid u is replaced with t, polynucleotide(s) comprising (or consisting of) a complementary sequence thereof, a polynucleotide(s) hybridizing under stringent conditions to any of these polynucleotides, or a variant(s) or a fragment(s) comprising 15 or more consecutive nucleotides of any of these polynucleotide sequences.

(367) The kit or the device of the present invention can further comprise one or more polynucleotides comprising (or consisting of), for example, a nucleotide sequence represented by any of SEQ ID NOs: 164 to 329, or a nucleotide sequence derived from the nucleotide sequence in which the nucleic acid u is replaced with t, a polynucleotide(s) comprising (or consisting of) a complementary sequence thereof, a polynucleotide(s) hybridizing under stringent conditions to any of these polynucleotides, a variant(s) or a fragment(s) comprising 15 or more consecutive nucleotides of any of these polynucleotide sequences.

(368) The fragment or fragments that can be comprised in the kit or the device of the present invention is/are, for example, one or more polynucleotides, preferably two or more polynucleotides, selected from the group consisting of the following polynucleotides (1) and (2):

(369) (1) a polynucleotide comprising 15 or more consecutive nucleotides derived from a nucleotide sequence represented by any of SEQ ID NOs: 1 to 163 in which the nucleic acid u is replaced with t, or a complementary sequence thereof; and

(370) (2) a polynucleotide comprising 15 or more consecutive nucleotides derived from a nucleotide sequence represented by any of SEQ ID NOs: 164 to 329 in which the nucleic acid u is replaced with t, or a complementary sequence thereof.

(371) In a preferred embodiment, the polynucleotide is a polynucleotide consisting of a nucleotide sequence represented by any of SEQ ID NOs: 1 to 163, or a nucleotide sequence derived from the nucleotide sequence in which the nucleic acid u is replaced with t, a polynucleotide consisting of a complementary sequence thereof, a polynucleotide hybridizing under stringent conditions to any of these polynucleotides, or a variant thereof comprising 15 or more, preferably 17 or more, more preferably 19 or more consecutive nucleotides.

(372) In a preferred embodiment, the polynucleotide is a polynucleotide consisting of a nucleotide sequence represented by any of SEQ ID NOs: 164 to 329, or a nucleotide sequence derived from the nucleotide sequence in which the nucleic acid u is replaced with t, a polynucleotide consisting of a complementary sequence thereof, a polynucleotide hybridizing under stringent conditions to any of these polynucleotides, or a variant thereof comprising 15 or more, preferably 17 or more, more preferably 19 or more consecutive nucleotides.

(373) In a preferred embodiment, the fragment can be a polynucleotide comprising 15 or more, preferably 17 or more, more preferably 19 or more consecutive nucleotides.

(374) In the present invention, the size of the polynucleotide fragment is the number of nucleotides in the range from, for example, 15 consecutive nucleotides to less than the total number of nucleotides of the sequence, from 17 consecutive nucleotides to less than the total number of nucleotides of the sequence, or from 19 consecutive nucleotides to less than the total number of nucleotides of the sequence, in the nucleotide sequence of each polynucleotide.

(375) Examples of the combination of the above-mentioned polynucleotides as target nucleic acids in the kit or the device of the present invention can include a single (one) polynucleotide or combinations of 2, 3, 4, 5, 6, 7, 8, 9, 10 or more of the above-mentioned polynucleotides consisting of the nucleotide sequences represented by SEQ ID NOs: 1 to 329 as shown in Table 1 above. However, these are given merely for illustrative purposes, and all of various other possible combinations are included in the present invention.

(376) Examples of the combinations of target nucleic acids in the kit or the device for discriminating lung cancer patients from test subjects without lung cancer, such as healthy subjects, benign bone and soft tissue tumor patients and benign breast disease patients, or patients having a cancer other than lung cancer, according to the present invention can include combinations of two or more of the above-mentioned polynucleotides consisting of the nucleotide sequences represented by SEQ ID NOs as shown in Table 1. For example, any two or more of the above-mentioned polynucleotides consisting of nucleotide sequences represented by SEQ ID NOs: 1 to 329 can be combined. Among them, at least one polynucleotide of the newly found polynucleotides consisting of the nucleotide sequences represented by SEQ ID NOs: 1 to 163 is preferably selected. Among them, particularly, a combination comprising at least one polynucleotide selected from the group consisting of the polynucleotides of SEQ ID NOs: 18, 4, 130, 2, 9, 17, and 121 (hereinafter, this group is referred to as “cancer type-specific polynucleotide group”) is more preferred.

(377) Non-limiting examples of the combination comprising the polynucleotide consisting of the nucleotide sequence represented by SEQ ID NO: 18 or a complementary sequence thereof are listed below as combinations of target nucleic acids:

(378) (1) a combination of SEQ ID NOs: 18, and 164;

(379) (2) a combination of SEQ ID NOs: 18, 164, and 255;

(380) (3) a combination of SEQ ID NOs: 18, 164, and 300;

(381) (4) a combination of SEQ ID NOs: 18, 164, and 190;

(382) (5) a combination of SEQ ID NOs: 18, 85, and 164;

(383) (6) a combination of SEQ ID NOs: 18, 147, and 164;

(384) (7) a combination of SEQ ID NOs: 18, 22, and 164;

(385) (8) a combination of SEQ ID NOs: 18, 164, and 312;

(386) (9) a combination of SEQ ID NOs: 18, 66, and 164;

(387) (10) a combination of SEQ ID NOs: 18, 78, and 164;

(388) (11) a combination of SEQ ID NOs: 18, 27, and 164;

(389) (12) a combination of SEQ ID NOs: 18, 164, and 207;

(390) (13) a combination of SEQ ID NOs: 18, 82, and 164;

(391) (14) a combination of SEQ ID NOs: 18, 164, and 263;

(392) (15) a combination of SEQ ID NOs: 18, 164, and 168;

(393) (16) a combination of SEQ ID NOs: 18, 34, and 164;

(394) (17) a combination of SEQ ID NOs: 18, 39, and 164;

(395) (18) a combination of SEQ ID NOs: 18, 57, and 164;

(396) (19) a combination of SEQ ID NOs: 18, 121, and 164;

(397) (20) a combination of SEQ ID NOs: 18, 107, and 164;

(398) (21) a combination of SEQ ID NOs: 18, 70, and 164;

(399) (22) a combination of SEQ ID NOs: 18, 50, and 164;

(400) (23) a combination of SEQ ID NOs: 18, 164, and 250;

(401) (24) a combination of SEQ ID NOs: 18, 164, and 315;

(402) (25) a combination of SEQ ID NOs: 18, 164, and 211;

(403) (26) a combination of SEQ ID NOs: 18, 164, and 326;

(404) (27) a combination of SEQ ID NOs: 18, 164, and 308;

(405) (28) a combination of SEQ ID NOs: 18, 164, and 268;

(406) (29) a combination of SEQ ID NOs: 18, 164, and 191;

(407) (30) a combination of SEQ ID NOs: 18, 149, and 165;

(408) (31) a combination of SEQ ID NOs: 18, 121, 130, and 164;

(409) (32) a combination of SEQ ID NOs: 18, 164, 255, and 316;

(410) (33) a combination of SEQ ID NOs: 18, 121, 164, and 255;

(411) (34) a combination of SEQ ID NOs: 18, 147, 164, and 255;

(412) (35) a combination of SEQ ID NOs: 18, 27, 164, and 255;

(413) (36) a combination of SEQ ID NOs: 18, 34, 164, and 255;

(414) (37) a combination of SEQ ID NOs: 18, 47, 164, and 255;

(415) (38) a combination of SEQ ID NOs: 18, 158, 164, and 255;

(416) (39) a combination of SEQ ID NOs: 18, 164, 220, and 255;

(417) (40) a combination of SEQ ID NOs: 18, 88, 164, and 255;

(418) (41) a combination of SEQ ID NOs: 18, 130, 164, and 268;

(419) (42) a combination of SEQ ID NOs: 18, 164, 255, and 321;

(420) (43) a combination of SEQ ID NOs: 18, 164, 184, and 255;

(421) (44) a combination of SEQ ID NOs: 18, 152, 164, and 255;

(422) (45) a combination of SEQ ID NOs: 18, 164, 185, and 255;

(423) (46) a combination of SEQ ID NOs: 18, 164, 238, and 255;

(424) (47) a combination of SEQ ID NOs: 18, 164, 255, and 256;

(425) (48) a combination of SEQ ID NOs: 18, 127, 164, and 255;

(426) (49) a combination of SEQ ID NOs: 18, 164, 222, and 255;

(427) (50) a combination of SEQ ID NOs: 18, 139, 164, and 255;

(428) (51) a combination of SEQ ID NOs: 18, 39, 164, and 255;

(429) (52) a combination of SEQ ID NOs: 18, 164, 255, and 295;

(430) (53) a combination of SEQ ID NOs: 18, 146, 164, and 255;

(431) (54) a combination of SEQ ID NOs: 18, 164, 211, and 255;

(432) (55) a combination of SEQ ID NOs: 18, 164, 255, and 322;

(433) (56) a combination of SEQ ID NOs: 18, 164, 255, and 318;

(434) (57) a combination of SEQ ID NOs: 18, 121, 164, and 201;

(435) (58) a combination of SEQ ID NOs: 18, 147, 164, and 300;

(436) (59) a combination of SEQ ID NOs: 18, 121, 151, and 164;

(437) (60) a combination of SEQ ID NOs: 18, 164, 211, and 300;

(438) (61) a combination of SEQ ID NOs: 18, 95, 164, and 268;

(439) (62) a combination of SEQ ID NOs: 18, 164, 231, and 268;

(440) (63) a combination of SEQ ID NOs: 18, 147, 164, and 268;

(441) (64) a combination of SEQ ID NOs: 18, 164, 188, and 268;

(442) (65) a combination of SEQ ID NOs: 18, 164, 268, and 312;

(443) (66) a combination of SEQ ID NOs: 18, 39, 164, and 300;

(444) (67) a combination of SEQ ID NOs: 18, 95, 121, and 164;

(445) (68) a combination of SEQ ID NOs: 18, 93, 164, and 268;

(446) (69) a combination of SEQ ID NOs: 18, 164, 268, and 308;

(447) (70) a combination of SEQ ID NOs: 18, 107, 121, and 164;

(448) (71) a combination of SEQ ID NOs: 18, 164, 218, and 268;

(449) (72) a combination of SEQ ID NOs: 18, 164, 202, and 268;

(450) (73) a combination of SEQ ID NOs: 13, 18, 130, and 165;

(451) (74) a combination of SEQ ID NOs: 18, 149, 165, and 168;

(452) (75) a combination of SEQ ID NOs: 18, 164, 242, and 268;

(453) (76) a combination of SEQ ID NOs: 18, 164, 214, and 268;

(454) (77) a combination of SEQ ID NOs: 18, 164, 268, and 313;

(455) (78) a combination of SEQ ID NOs: 18, 162, 164, and 268;

(456) (79) a combination of SEQ ID NOs: 18, 150, 164, and 268;

(457) (80) a combination of SEQ ID NOs: 18, 164, 268, and 315;

(458) (81) a combination of SEQ ID NOs: 18, 152, 164, and 268;

(459) (82) a combination of SEQ ID NOs: 18, 164, 268, and 325;

(460) (83) a combination of SEQ ID NOs: 18, 121, 149, and 165;

(461) (84) a combination of SEQ ID NOs: 13, 18, 165, and 260;

(462) (85) a combination of SEQ ID NOs: 13, 18, 165, and 268;

(463) (86) a combination of SEQ ID NOs: 13, 18, 121, and 165;

(464) (87) a combination of SEQ ID NOs: 13, 18, 165, and 168;

(465) (88) a combination of SEQ ID NOs: 18, 149, 165, and 268;

(466) (89) a combination of SEQ ID NOs: 13, 18, 83, and 165;

(467) (90) a combination of SEQ ID NOs: 13, 18, 165, and 263;

(468) (91) a combination of SEQ ID NOs: 2, 18, 165, and 268;

(469) (92) a combination of SEQ ID NOs: 13, 18, 165, and 211;

(470) (93) a combination of SEQ ID NOs: 13, 18, 165, and 256;

(471) (94) a combination of SEQ ID NOs: 13, 18, 165, and 276;

(472) (95) a combination of SEQ ID NOs: 13, 18, 165, and 302;

(473) (96) a combination of SEQ ID NOs: 13, 18, 165, and 190;

(474) (97) a combination of SEQ ID NOs: 18, 121, 130, 136, and 164;

(475) (98) a combination of SEQ ID NOs: 18, 121, 130, 164, and 314;

(476) (99) a combination of SEQ ID NOs: 18, 114, 121, 130, and 164;

(477) (100) a combination of SEQ ID NOs: 18, 121, 130, 164, and 214;

(478) (101) a combination of SEQ ID NOs: 18, 121, 130, 164, and 193;

(479) (102) a combination of SEQ ID NOs: 18, 130, 164, 255, and 268;

(480) (103) a combination of SEQ ID NOs: 18, 121, 130, 164, and 320;

(481) (104) a combination of SEQ ID NOs: 18, 121, 130, 164, and 301;

(482) (105) a combination of SEQ ID NOs: 18, 121, 130, 144, and 164;

(483) (106) a combination of SEQ ID NOs: 18, 121, 130, 164, and 168;

(484) (107) a combination of SEQ ID NOs: 18, 121, 130, 164, and 205;

(485) (108) a combination of SEQ ID NOs: 18, 121, 130, 158, and 164;

(486) (109) a combination of SEQ ID NOs: 18, 121, 130, 164, and 260;

(487) (110) a combination of SEQ ID NOs: 18, 106, 121, 130, and 164;

(488) (111) a combination of SEQ ID NOs: 18, 121, 130, 164, and 318;

(489) (112) a combination of SEQ ID NOs: 18, 121, 130, 164, and 286;

(490) (113) a combination of SEQ ID NOs: 18, 121, 130, 164, and 315;

(491) (114) a combination of SEQ ID NOs: 18, 121, 130, 164, and 237;

(492) (115) a combination of SEQ ID NOs: 18, 121, 130, 164, and 184;

(493) (116) a combination of SEQ ID NOs: 18, 121, 130, 164, and 270;

(494) (117) a combination of SEQ ID NOs: 18, 121, 130, 164, and 309;

(495) (118) a combination of SEQ ID NOs: 18, 121, 130, 164, and 278;

(496) (119) a combination of SEQ ID NOs: 18, 82, 121, 130, and 164;

(497) (120) a combination of SEQ ID NOs: 18, 23, 121, 130, and 164;

(498) (121) a combination of SEQ ID NOs: 18, 121, 130, 164, and 189;

(499) (122) a combination of SEQ ID NOs: 18, 121, 130, 152, and 164;

(500) (123) a combination of SEQ ID NOs: 18, 121, 130, 164, and 213;

(501) (124) a combination of SEQ ID NOs: 18, 121, 130, 164, and 229;

(502) (125) a combination of SEQ ID NOs: 18, 57, 121, 130, and 164;

(503) (126) a combination of SEQ ID NOs: 18, 121, 130, 142, and 164;

(504) (127) a combination of SEQ ID NOs: 18, 121, 130, 155, and 164;

(505) (128) a combination of SEQ ID NOs: 18, 39, 121, 130, and 164;

(506) (129) a combination of SEQ ID NOs: 18, 27, 130, 164, and 268;

(507) (130) a combination of SEQ ID NOs: 18, 33, 121, 130, and 164;

(508) (131) a combination of SEQ ID NOs: 18, 121, 126, 130, and 164;

(509) (132) a combination of SEQ ID NOs: 18, 121, 130, 164, and 319;

(510) (133) a combination of SEQ ID NOs: 18, 22, 121, 130, and 164;

(511) (134) a combination of SEQ ID NOs: 18, 59, 121, 130, and 164;

(512) (135) a combination of SEQ ID NOs: 18, 27, 121, 130, and 164;

(513) (136) a combination of SEQ ID NOs: 18, 130, 164, 268, and 317;

(514) (137) a combination of SEQ ID NOs: 18, 121, 130, 164, and 201;

(515) (138) a combination of SEQ ID NOs: 18, 34, 164, 211, and 255;

(516) (139) a combination of SEQ ID NOs: 18, 19, 121, 130, and 164;

(517) (140) a combination of SEQ ID NOs: 18, 74, 130, 164, and 268;

(518) (141) a combination of SEQ ID NOs: 18, 130, 164, 264, and 268;

(519) (142) a combination of SEQ ID NOs: 18, 39, 164, 255, and 328;

(520) (143) a combination of SEQ ID NOs: 18, 39, 164, 226, and 255;

(521) (144) a combination of SEQ ID NOs: 18, 95, 121, 164, and 188;

(522) (145) a combination of SEQ ID NOs: 13, 18, 121, 130, and 165;

(523) (146) a combination of SEQ ID NOs: 13, 18, 130, 165, and 268;

(524) (147) a combination of SEQ ID NOs: 18, 151, 164, 268, and 315;

(525) (148) a combination of SEQ ID NOs: 18, 147, 164, 184, and 268;

(526) (149) a combination of SEQ ID NOs: 18, 149, 165, 168, and 268;

(527) (150) a combination of SEQ ID NOs: 13, 18, 165, 268, and 276;

(528) (151) a combination of SEQ ID NOs: 2, 18, 165, 268, and 301;

(529) (152) a combination of SEQ ID NOs: 2, 18, 165, 268, and 315;

(530) (153) a combination of SEQ ID NOs: 13, 18, 165, 183, and 268; and

(531) (154) a combination of SEQ ID NOs: 13, 18, 165, 184, and 268.

(532) Non-limiting examples of the combination comprising the polynucleotide consisting of the nucleotide sequence represented by SEQ ID NO: 4 or a complementary sequence thereof are further listed below as combinations of target nucleic acids:

(533) (1) a combination of SEQ ID NOs: 4, and 164;

(534) (2) a combination of SEQ ID NOs: 4, 165, and 168;

(535) (3) a combination of SEQ ID NOs: 4, 165, 168, and 246;

(536) (4) a combination of SEQ ID NOs: 4, 128, 165, and 168;

(537) (5) a combination of SEQ ID NOs: 4, 117, 165, and 168;

(538) (6) a combination of SEQ ID NOs: 4, 159, 165, and 168;

(539) (7) a combination of SEQ ID NOs: 4, 165, 168, and 260;

(540) (8) a combination of SEQ ID NOs: 4, 17, 165, and 168;

(541) (9) a combination of SEQ ID NOs: 4, 165, 168, and 173;

(542) (10) a combination of SEQ ID NOs: 4, 80, 165, and 168;

(543) (11) a combination of SEQ ID NOs: 4, 99, 165, and 168;

(544) (12) a combination of SEQ ID NOs: 2, 4, 168, and 246;

(545) (13) a combination of SEQ ID NOs: 4, 17, 115, and 168;

(546) (14) a combination of SEQ ID NOs: 4, 17, 115, and 302;

(547) (15) a combination of SEQ ID NOs: 4, 94, 173, and 183;

(548) (16) a combination of SEQ ID NOs: 2, 4, 173, and 183;

(549) (17) a combination of SEQ ID NOs: 2, 4, 115, and 168;

(550) (18) a combination of SEQ ID NOs: 4, 17, 115, and 184;

(551) (19) a combination of SEQ ID NOs: 4, 17, 165, 168, and 173;

(552) (20) a combination of SEQ ID NOs: 4, 17, 165, 168, and 223;

(553) (21) a combination of SEQ ID NOs: 4, 128, 129, 165, and 168;

(554) (22) a combination of SEQ ID NOs: 2, 4, 130, 168, and 246;

(555) (23) a combination of SEQ ID NOs: 4, 17, 128, 165, and 168;

(556) (24) a combination of SEQ ID NOs: 4, 17, 165, 168, and 169;

(557) (25) a combination of SEQ ID NOs: 4, 17, 117, 165, and 168;

(558) (26) a combination of SEQ ID NOs: 4, 17, 165, 168, and 323;

(559) (27) a combination of SEQ ID NOs: 4, 17, 81, 165, and 168;

(560) (28) a combination of SEQ ID NOs: 4, 17, 165, 168, and 253;

(561) (29) a combination of SEQ ID NOs: 4, 17, 162, 165, and 168;

(562) (30) a combination of SEQ ID NOs: 2, 4, 168, 201, and 246;

(563) (31) a combination of SEQ ID NOs: 4, 17, 141, 165, and 168;

(564) (32) a combination of SEQ ID NOs: 4, 17, 129, 165, and 168;

(565) (33) a combination of SEQ ID NOs: 4, 17, 165, 168, and 258;

(566) (34) a combination of SEQ ID NOs: 4, 17, 165, 168, and 190;

(567) (35) a combination of SEQ ID NOs: 4, 17, 115, 168, and 177;

(568) (36) a combination of SEQ ID NOs: 4, 17, 165, 168, and 191;

(569) (37) a combination of SEQ ID NOs: 4, 17, 158, 165, and 168;

(570) (38) a combination of SEQ ID NOs: 4, 17, 165, 168, and 184;

(571) (39) a combination of SEQ ID NOs: 4, 17, 94, 165, and 168;

(572) (40) a combination of SEQ ID NOs: 4, 17, 165, 168, and 296;

(573) (41) a combination of SEQ ID NOs: 4, 17, 165, 168, and 307;

(574) (42) a combination of SEQ ID NOs: 4, 17, 123, 165, and 168;

(575) (43) a combination of SEQ ID NOs: 4, 17, 39, 165, and 168;

(576) (44) a combination of SEQ ID NOs: 4, 17, 145, 165, and 168;

(577) (45) a combination of SEQ ID NOs: 4, 17, 165, 168, and 286;

(578) (46) a combination of SEQ ID NOs: 4, 17, 73, 165, and 168;

(579) (47) a combination of SEQ ID NOs: 4, 17, 115, 165, and 168;

(580) (48) a combination of SEQ ID NOs: 4, 17, 108, 165, and 168;

(581) (49) a combination of SEQ ID NOs: 4, 17, 156, 165, and 168;

(582) (50) a combination of SEQ ID NOs: 4, 17, 165, 168, and 249;

(583) (51) a combination of SEQ ID NOs: 4, 17, 131, 165, and 168;

(584) (52) a combination of SEQ ID NOs: 4, 17, 165, 168, and 304;

(585) (53) a combination of SEQ ID NOs: 4, 17, 157, 165, and 168;

(586) (54) a combination of SEQ ID NOs: 4, 17, 165, 168, and 318;

(587) (55) a combination of SEQ ID NOs: 4, 17, 74, 165, and 168;

(588) (56) a combination of SEQ ID NOs: 4, 17, 165, 168, and 216;

(589) (57) a combination of SEQ ID NOs: 4, 17, 165, 168, and 309;

(590) (58) a combination of SEQ ID NOs: 4, 17, 165, 168, and 236;

(591) (59) a combination of SEQ ID NOs: 4, 17, 165, 168, and 324;

(592) (60) a combination of SEQ ID NOs: 2, 4, 111, 168, and 173;

(593) (61) a combination of SEQ ID NOs: 4, 17, 115, 130, and 168;

(594) (62) a combination of SEQ ID NOs: 2, 4, 130, 168, and 173;

(595) (63) a combination of SEQ ID NOs: 4, 17, 111, 115, and 168;

(596) (64) a combination of SEQ ID NOs: 2, 4, 168, 173, and 201;

(597) (65) a combination of SEQ ID NOs: 4, 17, 115, 160, and 168;

(598) (66) a combination of SEQ ID NOs: 4, 17, 115, 168, and 246;

(599) (67) a combination of SEQ ID NOs: 2, 4, 115, 168, and 173;

(600) (68) a combination of SEQ ID NOs: 4, 17, 115, 168, and 201;

(601) (69) a combination of SEQ ID NOs: 4, 17, 115, 168, and 217;

(602) (70) a combination of SEQ ID NOs: 2, 4, 17, 115, and 168;

(603) (71) a combination of SEQ ID NOs: 4, 17, 115, 140, and 168; and

(604) (72) a combination of SEQ ID NOs: 4, 17, 102, 115, and 168.

(605) Non-limiting examples of the combination comprising the polynucleotide consisting of the nucleotide sequence represented by SEQ ID NO: 130 or a complementary sequence thereof are further listed below as combinations of target nucleic acids:

(606) (1) a combination of SEQ ID NOs: 121, 130, and 164;

(607) (2) a combination of SEQ ID NOs: 18, 121, 130, and 164;

(608) (3) a combination of SEQ ID NOs: 18, 130, 164, and 268;

(609) (4) a combination of SEQ ID NOs: 13, 18, 130, and 165;

(610) (5) a combination of SEQ ID NOs: 18, 121, 130, 136, and 164;

(611) (6) a combination of SEQ ID NOs: 18, 121, 130, 164, and 314;

(612) (7) a combination of SEQ ID NOs: 18, 114, 121, 130, and 164;

(613) (8) a combination of SEQ ID NOs: 18, 121, 130, 164, and 214;

(614) (9) a combination of SEQ ID NOs: 18, 121, 130, 164, and 193;

(615) (10) a combination of SEQ ID NOs: 18, 130, 164, 255, and 268;

(616) (11) a combination of SEQ ID NOs: 18, 121, 130, 164, and 320;

(617) (12) a combination of SEQ ID NOs: 18, 121, 130, 164, and 301;

(618) (13) a combination of SEQ ID NOs: 18, 121, 130, 144, and 164;

(619) (14) a combination of SEQ ID NOs: 18, 121, 130, 164, and 168;

(620) (15) a combination of SEQ ID NOs: 18, 121, 130, 164, and 205;

(621) (16) a combination of SEQ ID NOs: 18, 121, 130, 158, and 164;

(622) (17) a combination of SEQ ID NOs: 18, 121, 130, 164, and 260;

(623) (18) a combination of SEQ ID NOs: 18, 106, 121, 130, and 164;

(624) (19) a combination of SEQ ID NOs: 18, 121, 130, 164, and 318;

(625) (20) a combination of SEQ ID NOs: 18, 121, 130, 164, and 286;

(626) (21) a combination of SEQ ID NOs: 18, 121, 130, 164, and 315;

(627) (22) a combination of SEQ ID NOs: 18, 121, 130, 164, and 237;

(628) (23) a combination of SEQ ID NOs: 18, 121, 130, 164, and 184;

(629) (24) a combination of SEQ ID NOs: 18, 121, 130, 164, and 270;

(630) (25) a combination of SEQ ID NOs: 18, 121, 130, 164, and 309;

(631) (26) a combination of SEQ ID NOs: 18, 121, 130, 164, and 278;

(632) (27) a combination of SEQ ID NOs: 18, 82, 121, 130, and 164;

(633) (28) a combination of SEQ ID NOs: 18, 23, 121, 130, and 164;

(634) (29) a combination of SEQ ID NOs: 18, 121, 130, 164, and 189;

(635) (30) a combination of SEQ ID NOs: 18, 121, 130, 152, and 164;

(636) (31) a combination of SEQ ID NOs: 18, 121, 130, 164, and 213;

(637) (32) a combination of SEQ ID NOs: 18, 121, 130, 164, and 229;

(638) (33) a combination of SEQ ID NOs: 18, 57, 121, 130, and 164;

(639) (34) a combination of SEQ ID NOs: 18, 121, 130, 142, and 164;

(640) (35) a combination of SEQ ID NOs: 18, 121, 130, 155, and 164;

(641) (36) a combination of SEQ ID NOs: 18, 39, 121, 130, and 164;

(642) (37) a combination of SEQ ID NOs: 18, 27, 130, 164, and 268;

(643) (38) a combination of SEQ ID NOs: 18, 33, 121, 130, and 164;

(644) (39) a combination of SEQ ID NOs: 18, 121, 126, 130, and 164;

(645) (40) a combination of SEQ ID NOs: 18, 121, 130, 164, and 319;

(646) (41) a combination of SEQ ID NOs: 18, 22, 121, 130, and 164;

(647) (42) a combination of SEQ ID NOs: 18, 59, 121, 130, and 164;

(648) (43) a combination of SEQ ID NOs: 18, 27, 121, 130, and 164;

(649) (44) a combination of SEQ ID NOs: 18, 130, 164, 268, and 317;

(650) (45) a combination of SEQ ID NOs: 18, 121, 130, 164, and 201;

(651) (46) a combination of SEQ ID NOs: 18, 19, 121, 130, and 164;

(652) (47) a combination of SEQ ID NOs: 18, 74, 130, 164, and 268;

(653) (48) a combination of SEQ ID NOs: 18, 130, 164, 264, and 268;

(654) (49) a combination of SEQ ID NOs: 2, 4, 130, 168, and 246;

(655) (50) a combination of SEQ ID NOs: 2, 9, 130, 168, and 246;

(656) (51) a combination of SEQ ID NOs: 13, 18, 121, 130, and 165;

(657) (52) a combination of SEQ ID NOs: 13, 18, 130, 165, and 268;

(658) (53) a combination of SEQ ID NOs: 4, 17, 115, 130, and 168;

(659) (54) a combination of SEQ ID NOs: 2, 4, 130, 168, and 173;

(660) (55) a combination of SEQ ID NOs: 2, 9, 130, 168, and 173;

(661) (56) a combination of SEQ ID NOs: 2, 111, 130, 168, and 173;

(662) (57) a combination of SEQ ID NOs: 2, 83, 130, 168, and 173;

(663) (58) a combination of SEQ ID NOs: 2, 6, 130, 168, and 173;

(664) (59) a combination of SEQ ID NOs: 2, 6, 130, 173, and 184;

(665) (60) a combination of SEQ ID NOs: 2, 130, 168, 173, and 213;

(666) (61) a combination of SEQ ID NOs: 2, 5, 130, 168, and 173; and

(667) (62) a combination of SEQ ID NOs: 2, 130, 168, 173, and 249.

(668) Non-limiting examples of the combination comprising the polynucleotide consisting of the nucleotide sequence represented by SEQ ID NO: 2 or a complementary sequence thereof are further listed below as combinations of target nucleic acids:

(669) (1) a combination of SEQ ID NOs: 2, 121, 165, and 168;

(670) (2) a combination of SEQ ID NOs: 2, 165, 168, and 268;

(671) (3) a combination of SEQ ID NOs: 2, 4, 168, and 246;

(672) (4) a combination of SEQ ID NOs: 2, 18, 165, and 268;

(673) (5) a combination of SEQ ID NOs: 2, 4, 173, and 183;

(674) (6) a combination of SEQ ID NOs: 2, 4, 115, and 168;

(675) (7) a combination of SEQ ID NOs: 2, 9, 168, and 246;

(676) (8) a combination of SEQ ID NOs: 2, 111, 168, and 246;

(677) (9) a combination of SEQ ID NOs: 2, 111, 168, and 173;

(678) (10) a combination of SEQ ID NOs: 2, 102, 168, and 246;

(679) (11) a combination of SEQ ID NOs: 2, 4, 130, 168, and 246;

(680) (12) a combination of SEQ ID NOs: 2, 4, 168, 201, and 246;

(681) (13) a combination of SEQ ID NOs: 2, 9, 130, 168, and 246;

(682) (14) a combination of SEQ ID NOs: 2, 4, 111, 168, and 173;

(683) (15) a combination of SEQ ID NOs: 2, 4, 130, 168, and 173;

(684) (16) a combination of SEQ ID NOs: 2, 4, 168, 173, and 201;

(685) (17) a combination of SEQ ID NOs: 2, 4, 115, 168, and 173;

(686) (18) a combination of SEQ ID NOs: 2, 9, 130, 168, and 173;

(687) (19) a combination of SEQ ID NOs: 2, 4, 17, 115, and 168;

(688) (20) a combination of SEQ ID NOs: 2, 111, 168, 173, and 268;

(689) (21) a combination of SEQ ID NOs: 2, 18, 165, 268, and 301;

(690) (22) a combination of SEQ ID NOs: 2, 18, 165, 268, and 315;

(691) (23) a combination of SEQ ID NOs: 2, 111, 130, 168, and 173;

(692) (24) a combination of SEQ ID NOs: 2, 83, 130, 168, and 173;

(693) (25) a combination of SEQ ID NOs: 2, 6, 130, 168, and 173;

(694) (26) a combination of SEQ ID NOs: 2, 111, 168, 173, and 223;

(695) (27) a combination of SEQ ID NOs: 2, 5, 111, 168, and 173;

(696) (28) a combination of SEQ ID NOs: 2, 6, 130, 173, and 184;

(697) (29) a combination of SEQ ID NOs: 2, 39, 111, 168, and 173;

(698) (30) a combination of SEQ ID NOs: 2, 111, 168, 173, and 222;

(699) (31) a combination of SEQ ID NOs: 2, 111, 152, 168, and 173;

(700) (32) a combination of SEQ ID NOs: 2, 111, 168, 173, and 241;

(701) (33) a combination of SEQ ID NOs: 2, 130, 168, 173, and 213;

(702) (34) a combination of SEQ ID NOs: 2, 111, 168, 173, and 184;

(703) (35) a combination of SEQ ID NOs: 2, 102, 111, 168, and 173;

(704) (36) a combination of SEQ ID NOs: 2, 5, 130, 168, and 173;

(705) (37) a combination of SEQ ID NOs: 2, 111, 168, 173, and 234;

(706) (38) a combination of SEQ ID NOs: 2, 111, 168, 173, and 230;

(707) (39) a combination of SEQ ID NOs: 2, 111, 168, 173, and 307;

(708) (40) a combination of SEQ ID NOs: 2, 130, 168, 173, and 249;

(709) (41) a combination of SEQ ID NOs: 2, 111, 158, 168, and 173; and

(710) (42) a combination of SEQ ID NOs: 2, 39, 168, 169, and 173.

(711) Non-limiting examples of the combination comprising the polynucleotide consisting of the nucleotide sequence represented by SEQ ID NO: 9 or a complementary sequence thereof are further listed below as combinations of target nucleic acids:

(712) (1) a combination of SEQ ID NOs: 9, 165, and 168;

(713) (2) a combination of SEQ ID NOs: 9, 165, 168, and 173;

(714) (3) a combination of SEQ ID NOs: 9, 128, 165, and 168;

(715) (4) a combination of SEQ ID NOs: 9, 17, 165, and 168;

(716) (5) a combination of SEQ ID NOs: 9, 80, 165, and 168;

(717) (6) a combination of SEQ ID NOs: 2, 9, 168, and 246;

(718) (7) a combination of SEQ ID NOs: 5, 9, 165, 168, and 173;

(719) (8) a combination of SEQ ID NOs: 9, 128, 129, 165, and 168;

(720) (9) a combination of SEQ ID NOs: 2, 9, 130, 168, and 246;

(721) (10) a combination of SEQ ID NOs: 9, 17, 159, 165, and 168;

(722) (11) a combination of SEQ ID NOs: 9, 17, 165, 168, and 173; and

(723) (12) a combination of SEQ ID NOs: 2, 9, 130, 168, and 173.

(724) Non-limiting examples of the combination comprising the polynucleotide consisting of the nucleotide sequence represented by SEQ ID NO: 17 or a complementary sequence thereof are further listed below as combinations of target nucleic acids:

(725) (1) a combination of SEQ ID NOs: 17, 164, and 168;

(726) (2) a combination of SEQ ID NOs: 4, 17, 165, and 168;

(727) (3) a combination of SEQ ID NOs: 9, 17, 165, and 168;

(728) (4) a combination of SEQ ID NOs: 4, 17, 115, and 168;

(729) (5) a combination of SEQ ID NOs: 4, 17, 115, and 302;

(730) (6) a combination of SEQ ID NOs: 4, 17, 115, and 184;

(731) (7) a combination of SEQ ID NOs: 4, 17, 165, 168, and 173;

(732) (8) a combination of SEQ ID NOs: 4, 17, 165, 168, and 223;

(733) (9) a combination of SEQ ID NOs: 4, 17, 128, 165, and 168;

(734) (10) a combination of SEQ ID NOs: 4, 17, 165, 168, and 169;

(735) (11) a combination of SEQ ID NOs: 4, 17, 117, 165, and 168;

(736) (12) a combination of SEQ ID NOs: 4, 17, 165, 168, and 323;

(737) (13) a combination of SEQ ID NOs: 4, 17, 81, 165, and 168;

(738) (14) a combination of SEQ ID NOs: 4, 17, 165, 168, and 253;

(739) (15) a combination of SEQ ID NOs: 4, 17, 162, 165, and 168;

(740) (16) a combination of SEQ ID NOs: 4, 17, 141, 165, and 168;

(741) (17) a combination of SEQ ID NOs: 4, 17, 129, 165, and 168;

(742) (18) a combination of SEQ ID NOs: 4, 17, 165, 168, and 258;

(743) (19) a combination of SEQ ID NOs: 4, 17, 165, 168, and 190;

(744) (20) a combination of SEQ ID NOs: 4, 17, 115, 168, and 177;

(745) (21) a combination of SEQ ID NOs: 4, 17, 165, 168, and 191;

(746) (22) a combination of SEQ ID NOs: 4, 17, 158, 165, and 168;

(747) (23) a combination of SEQ ID NOs: 4, 17, 165, 168, and 184;

(748) (24) a combination of SEQ ID NOs: 4, 17, 94, 165, and 168;

(749) (25) a combination of SEQ ID NOs: 4, 17, 165, 168, and 296;

(750) (26) a combination of SEQ ID NOs: 4, 17, 165, 168, and 307;

(751) (27) a combination of SEQ ID NOs: 4, 17, 123, 165, and 168;

(752) (28) a combination of SEQ ID NOs: 4, 17, 39, 165, and 168;

(753) (29) a combination of SEQ ID NOs: 4, 17, 145, 165, and 168;

(754) (30) a combination of SEQ ID NOs: 4, 17, 165, 168, and 286;

(755) (31) a combination of SEQ ID NOs: 4, 17, 73, 165, and 168;

(756) (32) a combination of SEQ ID NOs: 4, 17, 115, 165, and 168;

(757) (33) a combination of SEQ ID NOs: 4, 17, 108, 165, and 168;

(758) (34) a combination of SEQ ID NOs: 4, 17, 156, 165, and 168;

(759) (35) a combination of SEQ ID NOs: 4, 17, 165, 168, and 249;

(760) (36) a combination of SEQ ID NOs: 4, 17, 131, 165, and 168;

(761) (37) a combination of SEQ ID NOs: 4, 17, 165, 168, and 304;

(762) (38) a combination of SEQ ID NOs: 4, 17, 157, 165, and 168;

(763) (39) a combination of SEQ ID NOs: 4, 17, 165, 168, and 318;

(764) (40) a combination of SEQ ID NOs: 4, 17, 74, 165, and 168;

(765) (41) a combination of SEQ ID NOs: 4, 17, 165, 168, and 216;

(766) (42) a combination of SEQ ID NOs: 4, 17, 165, 168, and 309;

(767) (43) a combination of SEQ ID NOs: 4, 17, 165, 168, and 236;

(768) (44) a combination of SEQ ID NOs: 4, 17, 165, 168, and 324;

(769) (45) a combination of SEQ ID NOs: 9, 17, 159, 165, and 168;

(770) (46) a combination of SEQ ID NOs: 4, 17, 115, 130, and 168;

(771) (47) a combination of SEQ ID NOs: 4, 17, 111, 115, and 168;

(772) (48) a combination of SEQ ID NOs: 9, 17, 165, 168, and 173;

(773) (49) a combination of SEQ ID NOs: 4, 17, 115, 160, and 168;

(774) (50) a combination of SEQ ID NOs: 4, 17, 115, 168, and 246;

(775) (51) a combination of SEQ ID NOs: 4, 17, 115, 168, and 201;

(776) (52) a combination of SEQ ID NOs: 4, 17, 115, 168, and 217;

(777) (53) a combination of SEQ ID NOs: 2, 4, 17, 115, and 168;

(778) (54) a combination of SEQ ID NOs: 4, 17, 115, 140, and 168; and

(779) (55) a combination of SEQ ID NOs: 4, 17, 102, 115, and 168.

(780) Non-limiting examples of the combination comprising the polynucleotide consisting of the nucleotide sequence represented by SEQ ID NO: 121 or a complementary sequence thereof are further listed below as combinations of target nucleic acids:

(781) (1) a combination of SEQ ID NOs: 121, 130, and 164;

(782) (2) a combination of SEQ ID NOs: 18, 121, and 164;

(783) (3) a combination of SEQ ID NOs: 121, 164, and 168;

(784) (4) a combination of SEQ ID NOs: 121, 164, and 328;

(785) (5) a combination of SEQ ID NOs: 121, 164, and 211;

(786) (6) a combination of SEQ ID NOs: 95, 121, and 164;

(787) (7) a combination of SEQ ID NOs: 6, 121, and 165;

(788) (8) a combination of SEQ ID NOs: 18, 121, 130, and 164;

(789) (9) a combination of SEQ ID NOs: 18, 121, 164, and 255;

(790) (10) a combination of SEQ ID NOs: 18, 121, 164, and 201;

(791) (11) a combination of SEQ ID NOs: 18, 121, 151, and 164;

(792) (12) a combination of SEQ ID NOs: 18, 95, 121, and 164;

(793) (13) a combination of SEQ ID NOs: 18, 107, 121, and 164;

(794) (14) a combination of SEQ ID NOs: 2, 121, 165, and 168;

(795) (15) a combination of SEQ ID NOs: 18, 121, 149, and 165;

(796) (16) a combination of SEQ ID NOs: 13, 18, 121, and 165;

(797) (17) a combination of SEQ ID NOs: 18, 121, 130, 136, and 164;

(798) (18) a combination of SEQ ID NOs: 18, 121, 130, 164, and 314;

(799) (19) a combination of SEQ ID NOs: 18, 114, 121, 130, and 164;

(800) (20) a combination of SEQ ID NOs: 18, 121, 130, 164, and 214;

(801) (21) a combination of SEQ ID NOs: 18, 121, 130, 164, and 193;

(802) (22) a combination of SEQ ID NOs: 18, 121, 130, 164, and 320;

(803) (23) a combination of SEQ ID NOs: 18, 121, 130, 164, and 301;

(804) (24) a combination of SEQ ID NOs: 18, 121, 130, 144, and 164;

(805) (25) a combination of SEQ ID NOs: 18, 121, 130, 164, and 168;

(806) (26) a combination of SEQ ID NOs: 18, 121, 130, 164, and 205;

(807) (27) a combination of SEQ ID NOs: 18, 121, 130, 158, and 164;

(808) (28) a combination of SEQ ID NOs: 18, 121, 130, 164, and 260;

(809) (29) a combination of SEQ ID NOs: 18, 106, 121, 130, and 164;

(810) (30) a combination of SEQ ID NOs: 18, 121, 130, 164, and 318;

(811) (31) a combination of SEQ ID NOs: 18, 121, 130, 164, and 286;

(812) (32) a combination of SEQ ID NOs: 18, 121, 130, 164, and 315;

(813) (33) a combination of SEQ ID NOs: 18, 121, 130, 164, and 237;

(814) (34) a combination of SEQ ID NOs: 18, 121, 130, 164, and 184;

(815) (35) a combination of SEQ ID NOs: 18, 121, 130, 164, and 270;

(816) (36) a combination of SEQ ID NOs: 18, 121, 130, 164, and 309;

(817) (37) a combination of SEQ ID NOs: 18, 121, 130, 164, and 278;

(818) (38) a combination of SEQ ID NOs: 18, 82, 121, 130, and 164;

(819) (39) a combination of SEQ ID NOs: 18, 23, 121, 130, and 164;

(820) (40) a combination of SEQ ID NOs: 18, 121, 130, 164, and 189;

(821) (41) a combination of SEQ ID NOs: 18, 121, 130, 152, and 164;

(822) (42) a combination of SEQ ID NOs: 18, 121, 130, 164, and 213;

(823) (43) a combination of SEQ ID NOs: 18, 121, 130, 164, and 229;

(824) (44) a combination of SEQ ID NOs: 18, 57, 121, 130, and 164;

(825) (45) a combination of SEQ ID NOs: 18, 121, 130, 142, and 164;

(826) (46) a combination of SEQ ID NOs: 18, 121, 130, 155, and 164;

(827) (47) a combination of SEQ ID NOs: 18, 39, 121, 130, and 164;

(828) (48) a combination of SEQ ID NOs: 18, 33, 121, 130, and 164;

(829) (49) a combination of SEQ ID NOs: 18, 121, 126, 130, and 164;

(830) (50) a combination of SEQ ID NOs: 18, 121, 130, 164, and 319;

(831) (51) a combination of SEQ ID NOs: 18, 22, 121, 130, and 164;

(832) (52) a combination of SEQ ID NOs: 18, 59, 121, 130, and 164;

(833) (53) a combination of SEQ ID NOs: 18, 27, 121, 130, and 164;

(834) (54) a combination of SEQ ID NOs: 18, 121, 130, 164, and 201;

(835) (55) a combination of SEQ ID NOs: 18, 19, 121, 130, and 164;

(836) (56) a combination of SEQ ID NOs: 18, 95, 121, 164, and 188; and

(837) (57) a combination of SEQ ID NOs: 13, 18, 121, 130, and 165.

(838) Examples of the combinations of target nucleic acids in the kit or the device for discriminating lung adenocarcinoma patients from test subjects without lung cancer, such as healthy subjects, benign bone and soft tissue tumor patients and benign breast disease patients, or patients having a cancer other than lung cancer, according to the present invention can include combinations of two or more of the above-mentioned polynucleotides consisting of the nucleotide sequences represented by SEQ ID NOs as shown in Table 1. For example, any two or more of the above-mentioned polynucleotides consisting of nucleotide sequences represented by SEQ ID NOs: 1 to 329 can be combined. Among them, at least one polynucleotide of the newly found polynucleotides consisting of the nucleotide sequences represented by SEQ ID NOs: 1 to 163 is preferably selected.

(839) Examples of the combinations of target nucleic acids in the kit or the device for discriminating squamous cell carcinoma patients from test subjects without lung cancer, such as healthy subjects, benign bone and soft tissue tumor patients and benign breast disease patients, or patients having a cancer other than lung cancer, according to the present invention can include combinations of two or more of the above-mentioned polynucleotides consisting of the nucleotide sequences represented by SEQ ID NOs as shown in Table 1. For example, any two or more of the above-mentioned polynucleotides consisting of nucleotide sequences represented by SEQ ID NOs: 1 to 329 can be combined. Among them, at least one polynucleotide of the newly found polynucleotides consisting of the nucleotide sequences represented by SEQ ID NOs: 1 to 163 is preferably selected.

(840) Examples of the combinations of target nucleic acids in the kit or the device for discriminating large cell carcinoma patients from test subjects without lung cancer, such as healthy subjects, benign bone and soft tissue tumor patients and benign breast disease patients, or patients having a cancer other than lung cancer, according to the present invention can include combinations of two or more of the above-mentioned polynucleotides consisting of the nucleotide sequences represented by SEQ ID NOs as shown in Table 1. For example, any two or more of the above-mentioned polynucleotides consisting of nucleotide sequences represented by SEQ ID NOs: 1 to 329 can be combined. Among them, at least one polynucleotide of the newly found polynucleotides consisting of the nucleotide sequences represented by SEQ ID NOs: 1 to 163 is preferably selected.

(841) Examples of the combinations of target nucleic acids in the kit or the device for discriminating small cell carcinoma patients from test subjects without lung cancer, such as healthy subjects, benign bone and soft tissue tumor patients and benign breast disease patients, or patients having a cancer other than lung cancer, according to the present invention can include combinations of two or more of the above-mentioned polynucleotides consisting of the nucleotide sequences represented by SEQ ID NOs as shown in Table 1. For example, any two or more of the above-mentioned polynucleotides consisting of nucleotide sequences represented by SEQ ID NOs: 1 to 329 can be combined. Among them, at least one polynucleotide of the newly found polynucleotides consisting of the nucleotide sequences represented by SEQ ID NOs: 1 to 163 is preferably selected.

(842) The kit or device of the present invention can also comprise polynucleotide(s) which can detect lung cancer and are known in the art or will be found in the future in addition to the polynucleotide(s) (that can comprise variant(s), fragments, or derivative(s)) according to the present invention as described above.

(843) The kit or device of the present invention can also comprise an antibody for measuring a marker or markers for lung cancer examination known in the art, such as CEA and CYFRA21-1, in addition to the polynucleotide(s) according to the present invention as described above.

(844) These polynucleotides and variants thereof or fragments thereof contained in the kit of the present invention may be packaged in different containers either individually or in any combination.

(845) The kit of the present invention may comprise a kit for extracting nucleic acids (e.g., total RNA) from body fluids, cells, or tissues, a fluorescent material for labeling, an enzyme and a medium for nucleic acid amplification, an instruction manual, etc.

(846) The device of the present invention is a device for measurement of cancer markers in which nucleic acids such as the polynucleotides according to the present invention described above, variants thereof, derivatives thereof, or fragments thereof are bonded or attached to, for example, a solid phase. Examples of the material for the solid phase include plastics, paper, glass, and silicon. The material for the solid phase is preferably a plastic from the viewpoint of easy processability. The solid phase has any shape and is, for example, square, round, reed-shaped, or film-shaped. The device of the present invention includes, for example, a device for measurement by a hybridization technique. Specific examples thereof include blotting devices and nucleic acid arrays (e.g., microarrays, DNA chips, and RNA chips).

(847) The nucleic acid array technique is a technique which involves bonding or attaching the nucleic acids one by one by use of a method [e.g., a method of spotting the nucleic acids using a high-density dispenser called spotter or arrayer onto the surface of the solid phase surface-treated, if necessary, by coating with L-lysine or the introduction of a functional group such as an amino group or a carboxyl group, a method of spraying the nucleic acids onto the solid phase using an inkjet which injects very small liquid droplets by a piezoelectric element or the like from a nozzle, or a method of sequentially synthesizing nucleotides on the solid phase] to prepare an array such as a chip and measuring target nucleic acids through the use of hybridization using this array.

(848) The kit or the device of the present invention comprises nucleic acids capable of specifically binding to the polynucleotides of at least one, preferably at least two, more preferably at least three, most preferably at least five to all of the lung cancer marker miRNAs, respectively, of the group A described above, or to a polynucleotide(s) consisting of a nucleotide sequence(s) complementary to that of the polynucleotide(s). The kit or the device of the present invention can optionally further comprise nucleic acids capable of specifically binding to the polynucleotides of at least one, preferably at least two, more preferably at least three, most preferably at least five to all of the lung cancer marker miRNAs, respectively, of the group B described above, or to a polynucleotide(s) consisting of a nucleotide sequence(s) complementary to that of the polynucleotide(s).

(849) The kit or the device of the present invention can be used for detecting lung cancer as described in Section 4 below.

(850) 4. Method for Detecting Lung Cancer

(851) The present invention further provides a method for detecting lung cancer, using the above-mentioned nucleic acid(s) that can be used in the present invention (alternatively, e.g., the kit or the device of the present invention as described in Section 3 above) to measure one or more expression levels of lung cancer-derived genes represented by: miR-6787-5p, miR-920, miR-3622a-5p, miR-1185-1-3p, miR-4327, miR-5739, miR-937-5p, miR-1181, miR-1185-2-3p, miR-1193, miR-1207-5p, miR-1238-5p, miR-1246, miR-1249-5p, miR-1292-3p, miR-1469, miR-1470, miR-197-5p, miR-208a-5p, miR-2110, miR-211-3p, miR-2467-3p, miR-3122, miR-3141, miR-3156-5p, miR-3158-5p, miR-3160-5p, miR-3180-3p, miR-3191-3p, miR-3194-3p, miR-320b, miR-328-5p, miR-3610, miR-3619-3p, miR-3620-5p, miR-370-3p, miR-373-5p, miR-3917, miR-3937, miR-4259, miR-4281, miR-4294, miR-4419b, miR-4428, miR-4429, miR-4433a-3p, miR-4447, miR-4449, miR-4459, miR-4480, miR-4485-5p, miR-4486, miR-4488, miR-4489, miR-4505, miR-4513, miR-4515, miR-4530, miR-4535, miR-4635, miR-4640-5p, miR-4646-5p, miR-4656, miR-4663, miR-4665-5p, miR-4706, miR-4707-5p, miR-4708-3p, miR-4710, miR-4718, miR-4722-5p, miR-4727-3p, miR-4730, miR-4734, miR-4740-5p, miR-4747-3p, miR-4749-5p, miR-4755-3p, miR-4763-5p, miR-4787-3p, miR-5008-5p, miR-5010-5p, miR-504-3p, miR-5090, miR-5100, miR-5196-5p, miR-551b-5p, miR-557, miR-5787, miR-6090, miR-6124, miR-6132, miR-6510-5p, miR-6511b-5p, miR-6515-3p, miR-654-5p, miR-658, miR-668-5p, miR-6722-5p, miR-6724-5p, miR-6729-3p, miR-6737-5p, miR-6756-5p, miR-6762-5p, miR-6763-3p, miR-6766-5p, miR-6769a-5p, miR-6771-5p, miR-6786-5p, miR-6789-5p, miR-6794-5p, miR-6796-3p, miR-6797-5p, miR-6800-3p, miR-6802-5p, miR-6803-5p, miR-6805-3p, miR-6805-5p, miR-6807-5p, miR-6812-5p, miR-6819-5p, miR-6822-5p, miR-6824-5p, miR-6826-5p, miR-6850-5p, miR-6858-5p, miR-6861-5p, miR-6880-3p, miR-7107-5p, miR-7109-5p, miR-7114-5p, miR-7704, miR-7846-3p, miR-8052, miR-8060, miR-8071, miR-8073, miR-874-5p, miR-204-3p, miR-3154, miR-3960, miR-4433a-5p, miR-4455, miR-4462, miR-4476, miR-4508, miR-4687-3p, miR-4687-5p, miR-4732-5p, miR-4771, miR-642a-3p, miR-6732-5p, miR-6760-5p, miR-6799-5p, miR-6820-5p, miR-6821-5p, miR-6829-5p, miR-6893-5p, miR-7108-3p, miR-7111-5p, miR-8089, miR-885-3p, and miR-92b-3p; and optionally an expression level(s) of lung cancer-derived gene(s) represented by: miR-1343-3p, miR-6746-5p, miR-422a, miR-187-5p, miR-4632-5p, miR-6791-5p, miR-103a-3p, miR-107, miR-1199-5p, miR-1225-3p, miR-1225-5p, miR-1228-5p, miR-1229-5p, miR-1233-5p, miR-1237-5p, miR-1247-3p, miR-1249-3p, miR-1254, miR-1260b, miR-1268a, miR-1268b, miR-1273g-3p, miR-128-1-5p, miR-128-2-5p, miR-1290, miR-150-3p, miR-17-3p, miR-1908-5p, miR-1909-3p, miR-1914-3p, miR-1915-3p, miR-191-5p, miR-22-3p, miR-23b-3p, miR-24-3p, miR-296-3p, miR-296-5p, miR-3131, miR-3162-5p, miR-3188, miR-3196, miR-3197, miR-320a, miR-342-5p, miR-3621, miR-3648, miR-3656, miR-365a-5p, miR-3665, miR-3679-5p, miR-371a-5p, miR-3940-5p, miR-423-5p, miR-4257, miR-4270, miR-4271, miR-4286, miR-4298, miR-4417, miR-4442, miR-4446-3p, miR-4448, miR-4454, miR-4467, miR-4472, miR-4507, miR-4516, miR-451a, miR-4649-5p, miR-4651, miR-4665-3p, miR-4674, miR-4675, miR-4689, miR-4695-5p, miR-4697-5p, miR-4725-3p, miR-4739, miR-4745-5p, miR-4763-3p, miR-4792, miR-486-3p, miR-5001-5p, miR-5195-3p, miR-550a-5p, miR-5698, miR-6075, miR-6088, miR-6089, miR-6125, miR-6126, miR-614, miR-615-5p, miR-619-5p, miR-638, miR-642b-3p, miR-650, miR-663a, miR-663b, miR-6717-5p, miR-6721-5p, miR-6726-5p, miR-6727-5p, miR-6738-5p, miR-6741-5p, miR-6749-5p, miR-6752-5p, miR-675-5p, miR-6757-5p, miR-6763-5p, miR-6765-5p, miR-6775-5p, miR-6780b-5p, miR-6782-5p, miR-6784-5p, miR-6800-5p, miR-6806-5p, miR-6840-3p, miR-6848-5p, miR-6851-5p, miR-6870-5p, miR-6872-3p, miR-6875-5p, miR-6877-5p, miR-6879-5p, miR-6880-5p, miR-6885-5p, miR-6887-5p, miR-7108-5p, miR-711, miR-7113-3p, miR-744-5p, miR-760, miR-7845-5p, miR-7847-3p, miR-7977, miR-8059, miR-8063, miR-8072, miR-874-3p, miR-92a-2-5p, miR-92b-5p, miR-940, miR-1228-3p, miR-1275, miR-1307-3p, miR-1343-5p, miR-23a-3p, miR-29b-3p, miR-3135b, miR-3185, miR-4532, miR-4690-5p, miR-4758-5p, miR-4783-3p, miR-6131, miR-625-3p, miR-6511a-5p, miR-6765-3p, miR-6816-5p, miR-6825-5p, miR-6845-5p, miR-7150, miR-7641, miR-7975, and miR-92a-3p, in a sample, and evaluating in vitro whether or not the subject has lung cancer, based on the expression levels measured (and control expression levels of healthy subjects optionally measured in the same way as above). In the method, for example, using samples, such as blood, serum, or plasma, collected from a subject suspected of having lung cancer and a subject without lung cancer, the expression levels of the above mentioned genes obtained from these subjects are compared, and if the expression level(s) of the target nucleic acid(s) is different between these samples, the subject is evaluated to have lung cancer.

(852) This method of the present invention enables a limitedly invasive, early diagnosis of lung adenocarcinoma, lung squamous cell carcinoma, large cell lung carcinoma, small cell lung carcinoma and other lung cancers with high sensitivity and high specificity and thereby brings about early treatment and improved prognosis. In addition, the disease progression or the effectiveness of surgical, radiotherapeutic, and chemotherapeutic treatments can be monitored by the present invention.

(853) According to the present invention, the method for extracting the lung cancer-derived gene(s) from the sample such as blood, serum, or plasma prepared by the addition of a reagent for RNA extraction in 3D-Gene™ RNA extraction reagent from liquid sample kit (Toray Industries, Inc., Japan) is particularly preferable. A general acidic phenol method (acid guanidinium-phenol-chloroform (AGPC)) or Trizol™ (Life Technologies Corp.) may be used. The lung cancer-derived gene(s) may be also prepared by the addition of a reagent for RNA extraction containing acidic phenol, such as Trizol (Life Technologies Corp.) or Isogen (Nippon Gene Co., Ltd., Japan). Alternatively, a kit such as miRNeasy™ Mini Kit (Qiagen N.V.) may be used, although the method is not limited thereto.

(854) The present invention also provides use of the kit or the device of the present invention for detecting in vitro an expression product(s) of a lung cancer-derived miRNA gene(s) in a sample from a subject.

(855) In the method of the present invention, the kit or the device described above comprises a single polynucleotide or any possible combination of polynucleotides that can be used in the present invention as described above.

(856) In the detection or (genetic) diagnosis of lung cancer according to the present invention, each polynucleotide contained in the kit or the device of the present invention can be used as a probe or a primer. In the case of using the polynucleotides as primers, TaqMan™ MicroRNA Assays from Life Technologies Corp., miScript PCR System from Qiagen N.V., or the like can be used, although the method is not limited thereto.

(857) In the method of the present invention, measurement of the gene expression levels can be performed using the above-mentioned primers or probes according to a routine method in a method known in the art specifically for detecting particular genes, for example, a hybridization technique such as Northern blot, Southern blot, in situ hybridization, Northern hybridization, or Southern hybridization, a quantitative amplification technique such as quantitative RT-PCR, or a method with a next-generation sequencer. A body fluid such as blood, serum, plasma, or urine from a subject is collected as a sample to be assayed according to the type of the detection method used. Alternatively, total RNA prepared from such a body fluid by the method described above may be used, and various polynucleotides including cDNA prepared on the basis of the RNA may be used.

(858) The method, the kit or the device of the present invention is useful for diagnosis of lung cancer or the detection of the presence or absence of lung cancer. Specifically, the detection of lung cancer using the method, the kit or the device can be performed by detecting in vitro an expression level(s) of a gene(s) which is detected by the method or detected using the nucleic acid probe(s) or the primer(s) contained in the kit or the device, in a sample such as blood, serum, plasma, or urine from a subject suspected of having lung cancer. The subject suspected of having lung cancer can be evaluated as having lung cancer when the expression level(s) of a polynucleotide(s) consisting of a nucleotide sequence(s) represented by at least one of, for example, SEQ ID NOs: 1 to 163 and optionally a nucleotide sequence(s) represented by one or more of, for example, SEQ ID NOs: 164 to 329, as target nucleic acids, in the sample such as blood, serum, plasma, or urine of the subject, is significantly high in statistic compared to an expression level(s) of the nucleotide sequences in the sample such as blood, serum, or plasma, or urine of a subject without lung cancer (i.e., also referred to as a control animal).

(859) In the method of the present invention, or the method using the kit or the device of the present invention, the method for detecting the presence or the absence of lung cancer in a sample from a subject comprises collecting a body fluid such as blood, serum, plasma, or urine of a subject, and measuring the expression level(s) of the target gene(s) (or target nucleic acid(s)) contained therein using one or more polynucleotides (including a variant(s), a fragment(s), or a derivative(s)) selected from the groups of polynucleotides of the present invention, to evaluate the presence or absence of lung cancer or to detect lung cancer.

(860) The method for detecting lung cancer according to the present invention can be used in combination with an imaging test method such as chest X-ray examination, CT examination, MRI examination, or PET examination. The method for detecting lung cancer according to the present invention can also be used in combination with sputum cytology, pleural fluid analysis, bronchoscopy, percutaneous needle biopsy or the like, which is a pathological examination method involving the microscopic examination of collected cells or tissues. The method for detecting lung cancer according to the present invention is capable of specifically detecting lung cancer and therefore, can substantially discriminate lung cancer from cancer other than lung cancer and can determine lung cancer with higher reliability by combination with another examination method such as the imaging test method or the pathological examination method described above. Furthermore, the method of the present invention can also be utilized to confirm the necessity of carrying out another examination method such an imaging test or a pathological examination.

(861) The method for detecting lung cancer according to the present invention can also be used to evaluate or diagnose, for example, the presence or absence of amelioration of the disease or the degree of amelioration thereof in a lung cancer patient in the case that a lung cancer-related therapeutic drug which is known or on a development stage (including cisplatin, gefitinib, docetaxel, etoposide, carboplatin, paclitaxel, and combination drugs thereof as non-limiting examples) is administered to the patient for treatment or amelioration of the disease.

(862) The method of the present invention can comprise, for example, the following steps (a), (b), and (c):

(863) (a) a step of contacting in vitro a sample from a subject with a polynucleotide(s) contained in the kit or the device of the present invention;

(864) (b) a step of measuring an expression level(s) of the target nucleic acid(s) in the sample using the polynucleotide(s) as a nucleic acid probe(s) or primer(s); and

(865) (c) a step of evaluating the presence or absence of lung cancer (cells) in the subject on the basis of the measurement results in the step (b).

(866) In one embodiment, the present invention provides a method for detecting lung cancer, comprising: measuring an expression level(s) of a target nucleic acid(s) in a sample of a subject using a nucleic acid(s) capable of specifically binding to at least one, preferably at least two polynucleotides selected from the group consisting of the following miRNAs: miR-6787-5p, miR-920, miR-3622a-5p, miR-1185-1-3p, miR-4327, miR-5739, miR-937-5p, miR-1181, miR-1185-2-3p, miR-1193, miR-1207-5p, miR-1238-5p, miR-1246, miR-1249-5p, miR-1292-3p, miR-1469, miR-1470, miR-197-5p, miR-208a-5p, miR-2110, miR-211-3p, miR-2467-3p, miR-3122, miR-3141, miR-3156-5p, miR-3158-5p, miR-3160-5p, miR-3180-3p, miR-3191-3p, miR-3194-3p, miR-320b, miR-328-5p, miR-3610, miR-3619-3p, miR-3620-5p, miR-370-3p, miR-373-5p, miR-3917, miR-3937, miR-4259, miR-4281, miR-4294, miR-4419b, miR-4428, miR-4429, miR-4433a-3p, miR-4447, miR-4449, miR-4459, miR-4480, miR-4485-5p, miR-4486, miR-4488, miR-4489, miR-4505, miR-4513, miR-4515, miR-4530, miR-4535, miR-4635, miR-4640-5p, miR-4646-5p, miR-4656, miR-4663, miR-4665-5p, miR-4706, miR-4707-5p, miR-4708-3p, miR-4710, miR-4718, miR-4722-5p, miR-4727-3p, miR-4730, miR-4734, miR-4740-5p, miR-4747-3p, miR-4749-5p, miR-4755-3p, miR-4763-5p, miR-4787-3p, miR-5008-5p, miR-5010-5p, miR-504-3p, miR-5090, miR-5100, miR-5196-5p, miR-551b-5p, miR-557, miR-5787, miR-6090, miR-6124, miR-6132, miR-6510-5p, miR-6511b-5p, miR-6515-3p, miR-654-5p, miR-658, miR-668-5p, miR-6722-5p, miR-6724-5p, miR-6729-3p, miR-6737-5p, miR-6756-5p, miR-6762-5p, miR-6763-3p, miR-6766-5p, miR-6769a-5p, miR-6771-5p, miR-6786-5p, miR-6789-5p, miR-6794-5p, miR-6796-3p, miR-6797-5p, miR-6800-3p, miR-6802-5p, miR-6803-5p, miR-6805-3p, miR-6805-5p, miR-6807-5p, miR-6812-5p, miR-6819-5p, miR-6822-5p, miR-6824-5p, miR-6826-5p, miR-6850-5p, miR-6858-5p, miR-6861-5p, miR-6880-3p, miR-7107-5p, miR-7109-5p, miR-7114-5p, miR-7704, miR-7846-3p, miR-8052, miR-8060, miR-8071, miR-8073, miR-874-5p, miR-204-3p, miR-3154, miR-3960, miR-4433a-5p, miR-4455, miR-4462, miR-4476, miR-4508, miR-4687-3p, miR-4687-5p, miR-4732-5p, miR-4771, miR-642a-3p, miR-6732-5p, miR-6760-5p, miR-6799-5p, miR-6820-5p, miR-6821-5p, miR-6829-5p, miR-6893-5p, miR-7108-3p, miR-7111-5p, miR-8089, miR-885-3p, and miR-92b-3p, or to a polynucleotide(s) consisting of a nucleotide sequence(s) complementary to that of the polynucleotide(s); or a nucleic acid(s) for detecting the polynucleotide(s); and evaluating in vitro whether or not the subject has lung cancer using the above-measured expression levels and control expression levels of a subject(s) without lung cancer measured in the same way as above.

(867) As used herein, the term “evaluating” is evaluation support based on results of in vitro examination, not physician's judgment.

(868) As described above, in the method of the present invention, specifically, miR-6787-5p is hsa-miR-6787-5p, miR-920 is hsa-miR-920, miR-3622a-5p is hsa-miR-3622a-5p, miR-1185-1-3p is hsa-miR-1185-1-3p, miR-4327 is hsa-miR-4327, miR-5739 is hsa-miR-5739, miR-937-5p is hsa-miR-937-5p, miR-1181 is hsa-miR-1181, miR-1185-2-3p is hsa-miR-1185-2-3p, miR-1193 is hsa-miR-1193, miR-1207-5p is hsa-miR-1207-5p, miR-1238-5p is hsa-miR-1238-5p, miR-1246 is hsa-miR-1246, miR-1249-5p is hsa-miR-1249-5p, miR-1292-3p is hsa-miR-1292-3p, miR-1469 is hsa-miR-1469, miR-1470 is hsa-miR-1470, miR-197-5p is hsa-miR-197-5p, miR-208a-5p is hsa-miR-208a-5p, miR-2110 is hsa-miR-2110, miR-211-3p is hsa-miR-211-3p, miR-2467-3p is hsa-miR-2467-3p, miR-3122 is hsa-miR-3122, miR-3141 is hsa-miR-3141, miR-3156-5p is hsa-miR-3156-5p, miR-3158-5p is hsa-miR-3158-5p, miR-3160-5p is hsa-miR-3160-5p, miR-3180-3p is hsa-miR-3180-3p, miR-3191-3p is hsa-miR-3191-3p, miR-3194-3p is hsa-miR-3194-3p, miR-320b is hsa-miR-320b, miR-328-5p is hsa-miR-328-5p, miR-3610 is hsa-miR-3610, miR-3619-3p is hsa-miR-3619-3p, miR-3620-5p is hsa-miR-3620-5p, miR-370-3p is hsa-miR-370-3p, miR-373-5p is hsa-miR-373-5p, miR-3917 is hsa-miR-3917, miR-3937 is hsa-miR-3937, miR-4259 is hsa-miR-4259, miR-4281 is hsa-miR-4281, miR-4294 is hsa-miR-4294, miR-4419b is hsa-miR-4419b, miR-4428 is hsa-miR-4428, miR-4429 is hsa-miR-4429, miR-4433a-3p is hsa-miR-4433a-3p, miR-4447 is hsa-miR-4447, miR-4449 is hsa-miR-4449, miR-4459 is hsa-miR-4459, miR-4480 is hsa-miR-4480, miR-4485-5p is hsa-miR-4485-5p, miR-4486 is hsa-miR-4486, miR-4488 is hsa-miR-4488, miR-4489 is hsa-miR-4489, miR-4505 is hsa-miR-4505, miR-4513 is hsa-miR-4513, miR-4515 is hsa-miR-4515, miR-4530 is hsa-miR-4530, miR-4535 is hsa-miR-4535, miR-4635 is hsa-miR-4635, miR-4640-5p is hsa-miR-4640-5p, miR-4646-5p is hsa-miR-4646-5p, miR-4656 is hsa-miR-4656, miR-4663 is hsa-miR-4663, miR-4665-5p is hsa-miR-4665-5p, miR-4706 is hsa-miR-4706, miR-4707-5p is hsa-miR-4707-5p, miR-4708-3p is hsa-miR-4708-3p, miR-4710 is hsa-miR-4710, miR-4718 is hsa-miR-4718, miR-4722-5p is hsa-miR-4722-5p, miR-4727-3p is hsa-miR-4727-3p, miR-4730 is hsa-miR-4730, miR-4734 is hsa-miR-4734, miR-4740-5p is hsa-miR-4740-5p, miR-4747-3p is hsa-miR-4747-3p, miR-4749-5p is hsa-miR-4749-5p, miR-4755-3p is hsa-miR-4755-3p, miR-4763-5p is hsa-miR-4763-5p, miR-4787-3p is hsa-miR-4787-3p, miR-5008-5p is hsa-miR-5008-5p, miR-5010-5p is hsa-miR-5010-5p, miR-504-3p is hsa-miR-504-3p, miR-5090 is hsa-miR-5090, miR-5100 is hsa-miR-5100, miR-5196-5p is hsa-miR-5196-5p, miR-551b-5p is hsa-miR-551b-5p, miR-557 is hsa-miR-557, miR-5787 is hsa-miR-5787, miR-6090 is hsa-miR-6090, miR-6124 is hsa-miR-6124, miR-6132 is hsa-miR-6132, miR-6510-5p is hsa-miR-6510-5p, miR-6511b-5p is hsa-miR-6511b-5p, miR-6515-3p is hsa-miR-6515-3p, miR-654-5p is hsa-miR-654-5p, miR-658 is hsa-miR-658, miR-668-5p is hsa-miR-668-5p, miR-6722-5p is hsa-miR-6722-5p, miR-6724-5p is hsa-miR-6724-5p, miR-6729-3p is hsa-miR-6729-3p, miR-6737-5p is hsa-miR-6737-5p, miR-6756-5p is hsa-miR-6756-5p, miR-6762-5p is hsa-miR-6762-5p, miR-6763-3p is hsa-miR-6763-3p, miR-6766-5p is hsa-miR-6766-5p, miR-6769a-5p is hsa-miR-6769a-5p, miR-6771-5p is hsa-miR-6771-5p, miR-6786-5p is hsa-miR-6786-5p, miR-6789-5p is hsa-miR-6789-5p, miR-6794-5p is hsa-miR-6794-5p, miR-6796-3p is hsa-miR-6796-3p, miR-6797-5p is hsa-miR-6797-5p, miR-6800-3p is hsa-miR-6800-3p, miR-6802-5p is hsa-miR-6802-5p, miR-6803-5p is hsa-miR-6803-5p, miR-6805-3p is hsa-miR-6805-3p, miR-6805-5p is hsa-miR-6805-5p, miR-6807-5p is hsa-miR-6807-5p, miR-6812-5p is hsa-miR-6812-5p, miR-6819-5p is hsa-miR-6819-5p, miR-6822-5p is hsa-miR-6822-5p, miR-6824-5p is hsa-miR-6824-5p, miR-6826-5p is hsa-miR-6826-5p, miR-6850-5p is hsa-miR-6850-5p, miR-6858-5p is hsa-miR-6858-5p, miR-6861-5p is hsa-miR-6861-5p, miR-6880-3p is hsa-miR-6880-3p, miR-7107-5p is hsa-miR-7107-5p, miR-7109-5p is hsa-miR-7109-5p, miR-7114-5p is hsa-miR-7114-5p, miR-7704 is hsa-miR-7704, miR-7846-3p is hsa-miR-7846-3p, miR-8052 is hsa-miR-8052, miR-8060 is hsa-miR-8060, miR-8071 is hsa-miR-8071, miR-8073 is hsa-miR-8073, miR-874-5p is hsa-miR-874-5p, miR-204-3p is hsa-miR-204-3p, miR-3154 is hsa-miR-3154, miR-3960 is hsa-miR-3960, miR-4433a-5p is hsa-miR-4433a-5p, miR-4455 is hsa-miR-4455, miR-4462 is hsa-miR-4462, miR-4476 is hsa-miR-4476, miR-4508 is hsa-miR-4508, miR-4687-3p is hsa-miR-4687-3p, miR-4687-5p is hsa-miR-4687-5p, miR-4732-5p is hsa-miR-4732-5p, miR-4771 is hsa-miR-4771, miR-642a-3p is hsa-miR-642a-3p, miR-6732-5p is hsa-miR-6732-5p, miR-6760-5p is hsa-miR-6760-5p, miR-6799-5p is hsa-miR-6799-5p, miR-6820-5p is hsa-miR-6820-5p, miR-6821-5p is hsa-miR-6821-5p, miR-6829-5p is hsa-miR-6829-5p, miR-6893-5p is hsa-miR-6893-5p, miR-7108-3p is hsa-miR-7108-3p, miR-7111-5p is hsa-miR-7111-5p, miR-8089 is hsa-miR-8089, miR-885-3p is hsa-miR-885-3p, and miR-92b-3p is hsa-miR-92b-3p.

(869) Additionally, in one embodiment, the nucleic acid(s) (e.g., a probe(s) or a primer(s)) in the method of the present invention is selected from the group consisting of, for example, the following polynucleotides (a) to (e):

(870) (a) a polynucleotide consisting of a nucleotide sequence represented by any of SEQ ID NOs: 1 to 163, or a nucleotide sequence derived from the nucleotide sequence in which the nucleic acid u is replaced with t, a variant thereof, a derivative thereof, or a fragment thereof comprising 15 or more consecutive nucleotides;
(b) a polynucleotide comprising a nucleotide sequence represented by any of SEQ ID NOs: 1 to 163;
(c) a polynucleotide consisting of a nucleotide sequence complementary to a nucleotide sequence represented by any of SEQ ID NOs: 1 to 163, or a nucleotide sequence derived from the nucleotide sequence in which the nucleic acid u is replaced with t, a variant thereof, a derivative thereof, or a fragment thereof comprising 15 or more consecutive nucleotides;
(d) a polynucleotide comprising a nucleotide sequence complementary to a nucleotide sequence represented by any of SEQ ID NOs: 1 to 163, or a nucleotide sequence derived from the nucleotide sequence in which the nucleic acid u is replaced with t; and
(e) a polynucleotide hybridizing under stringent conditions to any of the polynucleotides (a) to (d).

(871) The nucleic acid(s) used in the method of the present invention can further comprise a nucleic acid(s) capable of specifically binding to at least one polynucleotide selected from the group consisting of the following miRNAs: miR-1343-3p, miR-6746-5p, miR-422a, miR-187-5p, miR-4632-5p, miR-6791-5p, miR-103a-3p, miR-107, miR-1199-5p, miR-1225-3p, miR-1225-5p, miR-1228-5p, miR-1229-5p, miR-1233-5p, miR-1237-5p, miR-1247-3p, miR-1249-3p, miR-1254, miR-1260b, miR-1268a, miR-1268b, miR-1273g-3p, miR-128-1-5p, miR-128-2-5p, miR-1290, miR-150-3p, miR-17-3p, miR-1908-5p, miR-1909-3p, miR-1914-3p, miR-1915-3p, miR-191-5p, miR-22-3p, miR-23b-3p, miR-24-3p, miR-296-3p, miR-296-5p, miR-3131, miR-3162-5p, miR-3188, miR-3196, miR-3197, miR-320a, miR-342-5p, miR-3621, miR-3648, miR-3656, miR-365a-5p, miR-3665, miR-3679-5p, miR-371a-5p, miR-3940-5p, miR-423-5p, miR-4257, miR-4270, miR-4271, miR-4286, miR-4298, miR-4417, miR-4442, miR-4446-3p, miR-4448, miR-4454, miR-4467, miR-4472, miR-4507, miR-4516, miR-451a, miR-4649-5p, miR-4651, miR-4665-3p, miR-4674, miR-4675, miR-4689, miR-4695-5p, miR-4697-5p, miR-4725-3p, miR-4739, miR-4745-5p, miR-4763-3p, miR-4792, miR-486-3p, miR-5001-5p, miR-5195-3p, miR-550a-5p, miR-5698, miR-6075, miR-6088, miR-6089, miR-6125, miR-6126, miR-614, miR-615-5p, miR-619-5p, miR-638, miR-642b-3p, miR-650, miR-663a, miR-663b, miR-6717-5p, miR-6721-5p, miR-6726-5p, miR-6727-5p, miR-6738-5p, miR-6741-5p, miR-6749-5p, miR-6752-5p, miR-675-5p, miR-6757-5p, miR-6763-5p, miR-6765-5p, miR-6775-5p, miR-6780b-5p, miR-6782-5p, miR-6784-5p, miR-6800-5p, miR-6806-5p, miR-6840-3p, miR-6848-5p, miR-6851-5p, miR-6870-5p, miR-6872-3p, miR-6875-5p, miR-6877-5p, miR-6879-5p, miR-6880-5p, miR-6885-5p, miR-6887-5p, miR-7108-5p, miR-711, miR-7113-3p, miR-744-5p, miR-760, miR-7845-5p, miR-7847-3p, miR-7977, miR-8059, miR-8063, miR-8072, miR-874-3p, miR-92a-2-5p, miR-92b-5p, miR-940, miR-1228-3p, miR-1275, miR-1307-3p, miR-1343-5p, miR-23a-3p, miR-29b-3p, miR-3135b, miR-3185, miR-4532, miR-4690-5p, miR-4758-5p, miR-4783-3p, miR-6131, miR-625-3p, miR-6511a-5p, miR-6765-3p, miR-6816-5p, miR-6825-5p, miR-6845-5p, miR-7150, miR-7641, miR-7975, and miR-92a-3p, or to a polynucleotide consisting of a nucleotide sequence complementary to that of the polynucleotide.

(872) Specifically, miR-1343-3p is hsa-miR-1343-3p, miR-6746-5p is hsa-miR-6746-5p, miR-422a is hsa-miR-422a, miR-187-5p is hsa-miR-187-5p, miR-4632-5p is hsa-miR-4632-5p, miR-6791-5p is hsa-miR-6791-5p, miR-103a-3p is hsa-miR-103a-3p, miR-107 is hsa-miR-107, miR-1199-5p is hsa-miR-1199-5p, miR-1225-3p is hsa-miR-1225-3p, miR-1225-5p is hsa-miR-1225-5p, miR-1228-5p is hsa-miR-1228-5p, miR-1229-5p is hsa-miR-1229-5p, miR-1233-5p is hsa-miR-1233-5p, miR-1237-5p is hsa-miR-1237-5p, miR-1247-3p is hsa-miR-1247-3p, miR-1249-3p is hsa-miR-1249-3p, miR-1254 is hsa-miR-1254, miR-1260b is hsa-miR-1260b, miR-1268a is hsa-miR-1268a, miR-1268b is hsa-miR-1268b, miR-1273g-3p is hsa-miR-1273g-3p, miR-128-1-5p is hsa-miR-128-1-5p, miR-128-2-5p is hsa-miR-128-2-5p, miR-1290 is hsa-miR-1290, miR-150-3p is hsa-miR-150-3p, miR-17-3p is hsa-miR-17-3p, miR-1908-5p is hsa-miR-1908-5p, miR-1909-3p is hsa-miR-1909-3p, miR-1914-3p is hsa-miR-1914-3p, miR-1915-3p is hsa-miR-1915-3p, miR-191-5p is hsa-miR-191-5p, miR-22-3p is hsa-miR-22-3p, miR-23b-3p is hsa-miR-23b-3p, miR-24-3p is hsa-miR-24-3p, miR-296-3p is hsa-miR-296-3p, miR-296-5p is hsa-miR-296-5p, miR-3131 is hsa-miR-3131, miR-3162-5p is hsa-miR-3162-5p, miR-3188 is hsa-miR-3188, miR-3196 is hsa-miR-3196, miR-3197 is hsa-miR-3197, miR-320a is hsa-miR-320a, miR-342-5p is hsa-miR-342-5p, miR-3621 is hsa-miR-3621, miR-3648 is hsa-miR-3648, miR-3656 is hsa-miR-3656, miR-365a-5p is hsa-miR-365a-5p, miR-3665 is hsa-miR-3665, miR-3679-5p is hsa-miR-3679-5p, miR-371a-5p is hsa-miR-371a-5p, miR-3940-5p is hsa-miR-3940-5p, miR-423-5p is hsa-miR-423-5p, miR-4257 is hsa-miR-4257, miR-4270 is hsa-miR-4270, miR-4271 is hsa-miR-4271, miR-4286 is hsa-miR-4286, miR-4298 is hsa-miR-4298, miR-4417 is hsa-miR-4417, miR-4442 is hsa-miR-4442, miR-4446-3p is hsa-miR-4446-3p, miR-4448 is hsa-miR-4448, miR-4454 is hsa-miR-4454, miR-4467 is hsa-miR-4467, miR-4472 is hsa-miR-4472, miR-4507 is hsa-miR-4507, miR-4516 is hsa-miR-4516, miR-451a is hsa-miR-451a, miR-4649-5p is hsa-miR-4649-5p, miR-4651 is hsa-miR-4651, miR-4665-3p is hsa-miR-4665-3p, miR-4674 is hsa-miR-4674, miR-4675 is hsa-miR-4675, miR-4689 is hsa-miR-4689, miR-4695-5p is hsa-miR-4695-5p, miR-4697-5p is hsa-miR-4697-5p, miR-4725-3p is hsa-miR-4725-3p, miR-4739 is hsa-miR-4739, miR-4745-5p is hsa-miR-4745-5p, miR-4763-3p is hsa-miR-4763-3p, miR-4792 is hsa-miR-4792, miR-486-3p is hsa-miR-486-3p, miR-5001-5p is hsa-miR-5001-5p, miR-5195-3p is hsa-miR-5195-3p, miR-550a-5p is hsa-miR-550a-5p, miR-5698 is hsa-miR-5698, miR-6075 is hsa-miR-6075, miR-6088 is hsa-miR-6088, miR-6089 is hsa-miR-6089, miR-6125 is hsa-miR-6125, miR-6126 is hsa-miR-6126, miR-614 is hsa-miR-614, miR-615-5p is hsa-miR-615-5p, miR-619-5p is hsa-miR-619-5p, miR-638 is hsa-miR-638, miR-642b-3p is hsa-miR-642b-3p, miR-650 is hsa-miR-650, miR-663a is hsa-miR-663a, miR-663b is hsa-miR-663b, miR-6717-5p is hsa-miR-6717-5p, miR-6721-5p is hsa-miR-6721-5p, miR-6726-5p is hsa-miR-6726-5p, miR-6727-5p is hsa-miR-6727-5p, miR-6738-5p is hsa-miR-6738-5p, miR-6741-5p is hsa-miR-6741-5p, miR-6749-5p is hsa-miR-6749-5p, miR-6752-5p is hsa-miR-6752-5p, miR-675-5p is hsa-miR-675-5p, miR-6757-5p is hsa-miR-6757-5p, miR-6763-5p is hsa-miR-6763-5p, miR-6765-5p is hsa-miR-6765-5p, miR-6775-5p is hsa-miR-6775-5p, miR-6780b-5p is hsa-miR-6780b-5p, miR-6782-5p is hsa-miR-6782-5p, miR-6784-5p is hsa-miR-6784-5p, miR-6800-5p is hsa-miR-6800-5p, miR-6806-5p is hsa-miR-6806-5p, miR-6840-3p is hsa-miR-6840-3p, miR-6848-5p is hsa-miR-6848-5p, miR-6851-5p is hsa-miR-6851-5p, miR-6870-5p is hsa-miR-6870-5p, miR-6872-3p is hsa-miR-6872-3p, miR-6875-5p is hsa-miR-6875-5p, miR-6877-5p is hsa-miR-6877-5p, miR-6879-5p is hsa-miR-6879-5p, miR-6880-5p is hsa-miR-6880-5p, miR-6885-5p is hsa-miR-6885-5p, miR-6887-5p is hsa-miR-6887-5p, miR-7108-5p is hsa-miR-7108-5p, miR-711 is hsa-miR-711, miR-7113-3p is hsa-miR-7113-3p, miR-744-5p is hsa-miR-744-5p, miR-760 is hsa-miR-760, miR-7845-5p is hsa-miR-7845-5p, miR-7847-3p is hsa-miR-7847-3p, miR-7977 is hsa-miR-7977, miR-8059 is hsa-miR-8059, miR-8063 is hsa-miR-8063, miR-8072 is hsa-miR-8072, miR-874-3p is hsa-miR-874-3p, miR-92a-2-5p is hsa-miR-92a-2-5p, miR-92b-5p is hsa-miR-92b-5p, miR-940 is hsa-miR-940, miR-1228-3p is hsa-miR-1228-3p, miR-1275 is hsa-miR-1275, miR-1307-3p is hsa-miR-1307-3p, miR-1343-5p is hsa-miR-1343-5p, miR-23a-3p is hsa-miR-23a-3p, miR-29b-3p is hsa-miR-29b-3p, miR-3135b is hsa-miR-3135b, miR-3185 is hsa-miR-3185, miR-4532 is hsa-miR-4532, miR-4690-5p is hsa-miR-4690-5p, miR-4758-5p is hsa-miR-4758-5p, miR-4783-3p is hsa-miR-4783-3p, miR-6131 is hsa-miR-6131, miR-625-3p is hsa-miR-625-3p, miR-6511a-5p is hsa-miR-6511a-5p, miR-6765-3p is hsa-miR-6765-3p, miR-6816-5p is hsa-miR-6816-5p, miR-6825-5p is hsa-miR-6825-5p, miR-6845-5p is hsa-miR-6845-5p, miR-7150 is hsa-miR-7150, miR-7641 is hsa-miR-7641, miR-7975 is hsa-miR-7975, and miR-92a-3p is hsa-miR-92a-3p.

(873) In one embodiment, the nucleic acid(s) may further be selected from, for example, the group consisting of the following polynucleotides (f) to (j):

(874) (f) a polynucleotide consisting of a nucleotide sequence represented by any of SEQ ID NOs: 164 to 329, or a nucleotide sequence derived from the nucleotide sequence in which the nucleic acid u is replaced with t, a variant thereof, a derivative thereof, or a fragment thereof comprising 15 or more consecutive nucleotides;
(g) a polynucleotide comprising a nucleotide sequence represented by any of SEQ ID NOs: 164 to 329;
(h) a polynucleotide consisting of a nucleotide sequence complementary to a nucleotide sequence represented by any of SEQ ID NOs: 164 to 329, or a nucleotide sequence derived from the nucleotide sequence in which the nucleic acid u is replaced with t, a variant thereof, a derivative thereof, or a fragment thereof comprising 15 or more consecutive nucleotides;
(i) a polynucleotide comprising a nucleotide sequence complementary to a nucleotide sequence represented by any of SEQ ID NOs: 164 to 329, or a nucleotide sequence derived from the nucleotide sequence in which the nucleic acid u is replaced with t; and
(j) a polynucleotide hybridizing under stringent conditions to any of the polynucleotides (f) to (i).

(875) Examples of the sample used in the method of the present invention can include samples prepared from living tissues (preferably lung tissues) or body fluids such as blood, serum, plasma, and urine from subjects. Specifically, for example, an RNA-containing sample prepared from the tissue, a polynucleotide-containing sample further prepared therefrom, a body fluid such as blood, serum, plasma, or urine, a portion or the whole of a living tissue collected from the subject by biopsy or the like, or a living tissue excised by surgery can be used, and the sample for measurement can be prepared therefrom.

(876) As used herein, the subject refers to a mammal, for example, a human, a monkey, a mouse, or a rat, without any limitation, and is preferably a human.

(877) The steps of the method of the present invention can be changed according to the type of the sample to be measured.

(878) In the case of using RNA as an analyte, the method for detecting lung cancer (cells) can comprise, for example, the following steps (a), (b), and (c):

(879) (a) a step of binding RNA prepared from a sample from a subject (wherein, for example, the 3′ end of the RNA may be polyadenylated for quantitative RT-PCR in step (b)) or complementary polynucleotides (cDNAs) transcribed from the RNA to a polynucleotide(s) in the kit of the present invention;
(b) a step of measuring the sample-derived RNA or the cDNAs synthesized from the RNA, which is/are bound to the polynucleotide(s), by hybridization using the polynucleotide(s) as a nucleic acid probe(s) or by quantitative RT-PCR using the polynucleotide(s) as a primer(s); and
(c) a step of evaluating the presence or absence of lung cancer (or lung cancer-derived gene) on the basis of the measurement results of the step (b).

(880) For example, various hybridization methods can be used for measuring the expression level(s) of a target gene(s), or detecting, examining, evaluating, or diagnosing lung cancer (or lung cancer-derived gene) in vitro according to the present invention. For example, Northern blot, Southern blot, DNA chip analysis, in situ hybridization, Northern hybridization, or Southern hybridization can be used as such a hybridization method. PCR such as quantitative RT-PCR can also be used in combination with hybridization method, or as an alternative thereof.

(881) In the case of using the Northern blot, the presence or absence of expression of each gene or the expression level thereof in the RNA can be detected or measured by use of, for example, the nucleic acid probe(s) that can be used in the present invention. Specific examples thereof can include a method which comprises labeling the nucleic acid probe (or a complementary strand) with a radioisotope (32P, 33P, 35S, etc.), a fluorescent material, or the like, hybridizing the labeled product with the tissue-derived RNA from a subject, which is transferred to a nylon membrane or the like according to a routine method, and then detecting and measuring a signal derived from the label (radioisotope or fluorescent material) on the formed DNA/RNA duplex using a radiation detector (examples thereof can include BAS-1800 II (Fujifilm Corp.)) or a fluorescence detector (examples thereof can include STORM 865 (GE Healthcare Japan Corp.)).

(882) In the case of using the quantitative RT-PCR, the presence or absence of expression of each gene or the expression level thereof in the RNA can be detected or measured by use of, for example, the primer that can be used in the present invention. Specific examples thereof can include a method which comprises recovering the tissue-derived RNA from a subject, preparing cDNAs according to reverse transcription using 3′-end polyadenylation treatment, specific primers, and the like, hybridizing a pair of primers (consisting of a plus strand and a reverse strand binding to the cDNA) prepared from the kit for detection of the present invention with the cDNA such that the region of each target gene marker can be amplified with the cDNA as a template, and performing PCR according to a routine method to detect the obtained single-stranded or double-stranded DNA. The method for detecting the single-stranded or double-stranded DNA can include a method of performing the PCR using the primers labeled in advance with a radioisotope or a fluorescent material, a method of electrophoresing the PCR product on an agarose gel and staining the double-stranded DNA with ethidium bromide or the like for detection, and a method of transferring the produced single-stranded or double-stranded DNA to a nylon membrane or the like according to a routine method and hybridizing the single-stranded or double-stranded DNA to a labeled nucleic acid probe for detection.

(883) In the case of using the nucleic acid array analysis, an RNA chip or a DNA chip in which the kit or device for detection of the present invention is attached as nucleic acid probes (single-stranded or double-stranded) to a substrate (solid phase), for example, is used. Regions having the attached nucleic acid probes are referred to as probe spots, and regions having no attached nucleic acid probe are referred to as blank spots. A group of genes immobilized on a solid-phase substrate is generally called a nucleic acid chip, a nucleic acid array, a microarray, or the like. The DNA or RNA array includes a DNA or RNA macroarray and a DNA or RNA microarray. In the present specification, the term “chip” includes these arrays. 3D-Gene™ Human miRNA Oligo chip (Toray Industries, Inc., Japan) can be used as the DNA chip, though the DNA chip is not limited thereto.

(884) Examples of the measurement using the DNA chip can include, but are not limited to, a method of detecting and measuring a signal derived from the label on the kit or device for detection using an image detector (examples thereof can include Typhoon 9410 (GE Healthcare) and 3D-Gene™ scanner (Toray Industries, Inc., Japan)).

(885) The “stringent conditions” used herein are, as mentioned above, conditions under which a nucleic acid probe hybridizes to its target sequence to a detectably larger extent (e.g., a measurement value equal to or larger than “(a mean of background measurement values)+(a standard error of the background measurement values)×2”) than that for other sequences.

(886) The stringent conditions are defined by hybridization and subsequent washing. Examples of the hybridization conditions include, but not limited to, 30° C. to 60° C. for 1 to 24 hours in a solution containing SSC, a surfactant, formamide, dextran sulfate, a blocking agent(s), etc. In this context, 1×SSC is an aqueous solution (pH 7.0) containing 150 mM sodium chloride and 15 mM sodium citrate. The surfactant includes, for example, SDS (sodium dodecyl sulfate), Triton, or Tween. The hybridization conditions more preferably comprise 3-10×SSC and 0.1-1% SDS. Examples of the conditions for the washing, following the hybridization, which is another condition to define the stringent conditions, can include conditions comprising continuous washing at 30° C. in a solution containing 0.5×SSC and 0.1% SDS, at 30° C. in a solution containing 0.2×SSC and 0.1% SDS, and at 30° C. in a 0.05×SSC solution. It is desirable that the complementary strand should maintain its hybridized state with a target plus strand even by washing under such conditions. Specifically, examples of such a complementary strand can include a strand consisting of a nucleotide sequence in a completely complementary relationship with the nucleotide sequence of the target plus (+) strand, and a strand consisting of a nucleotide sequence having at least 80%, preferably at least 85%, more preferably at least 90% or at least 95% identity to the strand.

(887) Other examples of the “stringent conditions” for the hybridization are described in, for example, Sambrook, J. & Russel, D., Molecular Cloning, A LABORATORY MANUAL, Cold Spring Harbor Laboratory Press, published on Jan. 15, 2001, Vol. 1, 7.42 to 7.45 and Vol. 2, 8.9 to 8.17, and can be used in the present invention.

(888) Examples of the conditions for carrying out PCR using polynucleotide fragments in the kit of the present invention as primers include treatment for approximately 15 seconds to 1 minute at 5 to 10° C. plus a Tm value calculated from the sequences of the primers, using a PCR buffer having composition such as 10 mM Tris-HCL (pH 8.3), 50 mM KCL, and 1 to 2 mM MgCl.sub.2. Examples of the method for calculating such a Tm value include Tm value=2×(the number of adenine residues+the number of thymine residues)+4×(the number of guanine residues+the number of cytosine residues).

(889) In the case of using the quantitative RT-PCR, a commercially available kit for measurement specially designed for quantitatively measuring miRNA, such as TaqMan™ MicroRNA Assays (Life Technologies Corp.), LNA™-based MicroRNA PCR (Exiqon), or Ncode™ miRNA qRT-PCT kit (Invitrogen Corp.) may be used.

(890) In the method of the present invention, measurement of the gene expression level(s) may be performed with a sequencer, in addition to hybridization methods described above. In use of a sequencer, any of DNA sequencers of the first generation based on Sanger method, the second generation with shorter read size, and the third generation with longer read size can be used (herein referred to as “next-generation sequencer”, including sequencers of the second generation and the third generation). For example, a commercially available measurement kit specifically designed for measuring miRNA using Miseq, Hiseq, or NexSeq (Illumina, Inc.); Ion Proton, Ion PGM, or Ion S5/S5 XL (Thermo Fisher Scientific Inc.); PacBio RS II or Sequel (Pacific Biosciences of California, Inc.); MinION (Oxford Nanopore Technologies Ltd.) exemplified in use of a Nanopore sequencer; or the like may be used.

(891) Next-generation sequencing is a method of obtaining sequence information using a next-generation sequencer, and characterized by being capable of simultaneously performing a huge number of sequencing reactions compared to Sanger method (e.g., Rick Kamps et al., Int. J. Mol. Sci., 2017, 18(2), p. 308 and Int. Neurourol. J., 2016, 20 (Suppl. 2), S76-83). Examples of next-generation sequencing steps for miRNA include, but not limited to, the following steps: at first, adaptor sequences having predetermined nucleotide sequences are attached, and all RNAs are reverse-transcribed into cDNAs before or after attachment of the sequences. After the reverse transcription, cDNAs derived from specific target miRNAs may be enriched or concentrated by PCR or the like or with a probe or the like, for analyzing the target miRNA before sequencing steps. Subsequent sequencing steps varies in detail depending on the type of a next-generation sequencer, but typically, a sequencing reaction is performed by linking to a substrate via an adaptor sequence and further using the adaptor sequence as a priming site. See details of the sequencing reaction, for example, in Rick Kamps et al. (see supra). Finally, the data are outputted. This step provides a collection of sequence information (reads) obtained by the sequencing reaction. For example, next-generation sequencing can identify a target miRNA(s) based on the sequence information, and measure the expression level thereof based on the number of reads having the sequences of the target miRNA(s).

(892) For the calculation of gene expression levels, statistical treatment described in, for example, Statistical analysis of gene expression microarray data (Speed T., Chapman and Hall/CRC), and A beginner's guide Microarray gene expression data analysis (Causton H. C. et al., Blackwell publishing) can be used in the present invention, though the calculation method is not limited thereto. For example, twice, preferably three times, more preferably six times the standard deviation of the measurement values of the blank spots are added to the average measurement value of the blank spots on the DNA chip, and probe spots having a signal value equal to or larger than the resulting value can be regarded as detected spots. Alternatively, the average measurement value of the blank spots is regarded as a background and can be subtracted from the measurement values of the probe spots to determine gene expression levels. A missing value for a gene expression level can be excluded from the analyte, preferably replaced with the smallest value of the gene expression level in each DNA chip, or more preferably replaced with a value obtained by subtracting 0.1 from a logarithmic value of the smallest value of the gene expression level. In order to eliminate low-signal genes, only genes that show gene expression levels of 2.sup.6, preferably 2.sup.8, more preferably 210 or larger in 20% or more, preferably 50% or more, more preferably 80% or more of the number of measurement samples can be selected as the analyte. Examples of the normalization of the gene expression level include, but are not limited to, global normalization and quantile normalization (Bolstad, B. M. et al., 2003, Bioinformatics, Vol. 19, p. 185-193).

(893) The present invention also provides a method of detecting a lung cancer (or assisting detection thereof) in a subject, comprising measuring target genes or gene expression levels in a sample from the subject using the gene markers (or target nucleic acids) of the present invention, the nucleic acids (or polynucleotides for detection or diagnosis), the kit, or the device (e.g., chip) for detecting the gene marker or a combination thereof; and assigning the expression levels of the target genes in a sample from the subject to a discriminant (discriminant function), which is prepared using gene expression levels of a sample(s) from a subject(s) (for example, a patient(s)) known to have a lung cancer and a sample(s) from a subject(s) (also referred to as control animal) having no lung cancer, as a training sample(s), and which can distinguishably discriminate the presence or absence of a lung cancer, thereby evaluating the presence or absence of the lung cancer, for example.

(894) Specifically, the present invention further provides the method comprising a first step of measuring in vitro expression levels of target genes, which are known to determine or evaluate that a subject has a lung cancer and/or not, in multiple samples, using the gene marker (or target nucleic acid) of the present invention, the nucleic acids (or polynucleotides for detection or diagnosis), the kit, the device (e.g., chip) for detecting the gene marker or a combination thereof; a second step of preparing a discriminant with the measurement values of the expression levels of the target genes obtained in the first step as training samples; a third step of measuring in vitro the expression levels of the target genes in a sample from the subject in the same manner as in the first step; and a fourth step of assigning the measurement values of the expression levels of the target genes obtained in the third step to the discriminant obtained in the second step, and determining or evaluating whether the subject has a lung cancer or not on the basis of the results obtained from the discriminant, for example. The above target genes are those that can be detected, for example, by the polynucleotides for detection or diagnosis, the polynucleotides contained in the kit or device, and variants thereof or fragments thereof.

(895) The discriminant herein can be prepared by use of any discriminant analysis method that can create a discriminant that distinguishably discriminate the presence or absence of a lung cancer, such as Fisher's discriminant analysis, nonlinear discriminant analysis based on the Mahalanobis' distance, neural network or Support Vector Machine (SVM), although the analysis method is not limited to these specific examples.

(896) When a clustering boundary is a straight line or a hyperplane, the linear discriminant analysis is a method for determining the belonging of a cluster using Formula 1 as a discriminant. In Formula 1, x represents an explanatory variable, w represents a coefficient of the explanatory variable, and w.sub.0 represents a constant term.

(897) $\begin{array}{cc}\left[\mathrm{Expression}1\right]& \\ f\left(x\right)=w_0+\underset{i=1}{\overset{n}{.Math.}}{w}_i{x}_i& \mathrm{Formula}1\end{array}$

(898) Values obtained from the discriminant are referred to as discriminant scores. The measurement values of a newly offered data set can be assigned as explanatory variables to the discriminant to determine clusters by the signs of the discriminant scores.

(899) The Fisher's discriminant analysis, a type of linear discriminant analysis, is a dimension-reducing method for selecting a dimension suitable for discriminating classes, and constructs a highly discriminating synthetic variable by focusing on the variance of the synthetic variables and minimizing the variance of data having the same label (Venables, W. N. et al., Modern Applied Statistics with S. Fourth edition. Springer, 2002). In the Fisher's discriminant analysis, direction w of projection is determined so as to maximize Formula 2. In this formula, μ represents an average input, ng represents the number of data belonging to class g, and μg represents an average input of the data belonging to class g. The numerator and the denominator are the interclass variance and the intraclass variance, respectively, when each of data is projected in the direction of the vector w. Discriminant coefficient w.sub.i is determined by maximizing this ratio (Takafumi Kanamori et al., “Pattern Recognition”, KYORITSU SHUPPAN CO., LTD. (Tokyo, Japan) (2009); Richard O. et al., Pattern Classification, Second Edition, Wiley-Interscience, 2000).

(900) $\begin{array}{cc}\left[\mathrm{Expression}2\right]& \\ J\left(w\right)=\frac{\underset{g=1}{\overset{G}{.Math.}}{n}_g\left(w^T{\mu }_g-w^T\mu \right){\left(w^T{\mu }_g-w^T\mu \right)}^T}{\underset{g=1}{\overset{G}{.Math.}}\underset{i:y_i=g}{.Math.}\left(w^T{x}_i-w^T{\mu }_g\right)\left(w^T{x}_i-w^T{\mu }_g\right)}\mathrm{subject}\mathrm{to}\mu =\underset{i=1}{\overset{n}{.Math.}}\frac{x_i}{n},{\mu }_g=\underset{i:u_i=g}{\overset{n}{.Math.}}\frac{x_i}{n_g}& \mathrm{Formula}2\end{array}$

(901) The Mahalanobis' distance is calculated according to Formula 3 in consideration of data correlation and can be used as nonlinear discriminant analysis for determining a cluster in which a data point belongs to, based on a short Mahalanobis' distance from the data point to that cluster. In Formula 3, μ represents a central vector of each cluster, and S.sup.−1 represents an inverse matrix of the variance-covariance matrix of the cluster. The central vector is calculated from explanatory variable x, and an average vector, a median value vector, or the like can be used.

(902) $\begin{array}{cc}\left[\mathrm{Expression}3\right]& \\ D\left(x,\mu \right)={\left\{{\left(x-\mu \right)}^t{S}^{-1}\left(x-\mu \right)\right\}}^{\frac{1}{2}}& \mathrm{Formula}3\end{array}$

(903) SVM is a discriminant analysis method devised by V. Vapnik (The Nature of Statistical Leaning Theory, Springer, 1995). Particular data points of a data set having known classes are defined as explanatory variables, and classes are defined as objective variables. A boundary plane called hyperplane for correctly classifying the data set into the known classes is determined, and a discriminant for data classification is determined using the boundary plane. Then, the measurement values of a newly offered data set can be assigned as explanatory variables to the discriminant to determine classes. In this respect, the result of the discriminant analysis may be classes, may be a probability of being classified into correct classes, or may be a distance from the hyperplane. In SVM, a method of nonlinearly converting a feature vector to a high dimension and performing linear discriminant analysis in the space is known as a method for tackling nonlinear problems. An expression in which an inner product of two factors in a nonlinearly mapped space is expressed only by inputs in their original spaces is called kernel. Examples of the kernel can include a linear kernel, a RBF (Radial Basis Function) kernel, and a Gaussian kernel. While highly dimensional mapping is performed according to the kernel, the optimum discriminant, i.e., a discriminant, can be actually constructed by mere calculation according to the kernel, which avoids calculating features in the mapped space (e.g., Hideki Aso et al., Frontier of Statistical Science 6 “Statistics of pattern recognition and learning—New concepts and approaches”, Iwanami Shoten, Publishers (Tokyo, Japan) (2004); Nello Cristianini et al., Introduction to SVM, Kyoritsu Shuppan Co., Ltd. (Tokyo, Japan) (2008)).

(904) C-support vector classification (C-SVC), a type of SVM, comprises preparing a hyperplane by training a data set with the explanatory variables of two groups and classifying an unknown data set into either of the groups (C. Cortes et al., 1995, Machine Learning, Vol. 20, p. 273-297).

(905) Exemplary calculation of the C-SVC discriminant that can be used in the method of the present invention will be given below. First, all subjects are divided into two groups, i.e., a group of lung cancer patients and a group of test subjects having no lung cancer. For example, lung tissue examination can be used for a reference under which each subject is confirmed to have a lung cancer or not.

(906) Next, a data set consisting of comprehensive gene expression levels of serum-derived samples of the two divided groups (hereinafter, this data set is referred to as a training cohort) is prepared, and a C-SVC discriminant is determined by using genes found to differ clearly in their gene expression levels between the two groups as explanatory variables and this grouping as objective variables (e.g., −1 and +1). An optimizing objective function is represented by Formula 4 wherein e represents all input vectors, y represents an objective variable, a represents a Lagrange's undetermined multiplier vector, Q represents a positive definite matrix, and C represents a parameter for adjusting constrained conditions.

(907) $\begin{array}{cc}\left[\mathrm{Expression}4\right]& \\ \underset{a}{\min }\frac{1}{2}{a}^T\mathrm{Qa}-e^{T}a\mathrm{subject}\mathrm{to}{y}^{T}a=0,0\le a_i\le C,i=1,\mathrm{.Math.},l,& \mathrm{Formula}4\end{array}$

(908) Formula 5 is a finally obtained discriminant, and a group in which the data point belongs to can be determined on the basis of the sign of a value obtained according to the discriminant. In this formula, x represents a support vector, y represents a label indicating the belonging of a group, a represents the corresponding coefficient, b represents a constant term, and K represents a kernel function.

(909) $\begin{array}{cc}\left[\mathrm{Expression}5\right]& \\ f\left(x\right)=\mathrm{sgn}\left(\underset{i=1}{\overset{l}{.Math.}}{y}_i{a}_{i}K\left(x_i,x\right)+b\right)& \mathrm{Formula}5\end{array}$

(910) For example, a RBF kernel defined by Formula 6 can be used as the kernel function. In this formula, x represents a support vector, and y represents a kernel parameter for adjusting the complexity of the hyperplane.
[Expression 6]
K(x.sub.i,x.sub.j)=exp(−r∥x.sub.i−x.sub.j∥.sup.2), r<0  Formula 6

(911) In addition, an approach such as neural network, k-nearest neighbor algorithms, decision trees, or logistic regression analysis can be selected as a method for determining or evaluating the presence or absence of lung cancer in a sample from a subject.

(912) In an embodiment, the method of the present invention can comprise, for example, the following steps (a), (b) and (c):

(913) (a) a step of measuring an expression level(s) of a target gene(s) in samples from subjects who are already known to have lung cancer or known to have no lung cancer, using the polynucleotide(s), the kit, or the device (e.g., DNA chip) for detection or diagnosis according to the present invention;

(914) (b) a step of preparing the discriminants of Formulas 1 to 3, 5 and 6 described above from the measurement values of the expression level determined in the step (a), and

(915) (c) a step of measuring an expression level(s) of the target gene(s) in a sample from a subject using the polynucleotide(s), the kit, or the device (e.g., DNA chip) for detection or diagnosis according to the present invention, and assigning the obtained measurement value(s) to the discriminants prepared in the step (b), and determining or evaluating that the subject has a lung cancer or not on the basis of the obtained results, or evaluating the expression level derived from a lung cancer patient by comparison with a control from a subject having no lung cancer (including, e.g., a healthy subject). In this context, in the discriminants of Formulas 1 to 3, 5 and 6, x represents an explanatory variable and includes a value obtained by measuring a polynucleotide(s) or a fragment(s) thereof selected from the polynucleotides serving as target nucleic acids described in Section 2 above. Specifically, the explanatory variable of the present invention for discriminating a lung cancer patient and a subject having no lung cancer is a gene expression level(s) selected from, for example, the following expression level (1) or (2).

(916) (1) a gene expression level(s) in the serum of a lung cancer patient and a subject having no lung cancer measured by any nucleic acid (e.g., DNA or RNA) comprising 15 or more consecutive nucleotides in the nucleotide sequence represented by any of SEQ ID NOs: 1 to 163 or a complementary sequence thereof; and

(917) (2) a gene expression level(s) in the serum of a lung cancer patient and a subject having no lung cancer measured by any nucleic acid (e.g., DNA or RNA) comprising 15 or more consecutive nucleotides in the nucleotide sequence represented by any of SEQ ID NOs: 164 to 329 or a complementary sequence thereof.

(918) As described above, as the method for determining or evaluating whether a subject has a lung cancer or not in a sample from the subject, it is necessary to use a discriminant employing one or more gene expression levels as an explanatory variable(s). In particular, for enhancing the discrimination accuracy of the discriminant using a single gene expression level alone, it is necessary to use a gene having a clear difference in expression level between two groups consisting of a group of lung cancer patients and a group of healthy subjects, in a discriminant.

(919) Specifically, the gene that is used for an explanatory variable of a discriminant is preferably determined as follows. First, using comprehensive gene expression levels of a group of lung cancer patients and comprehensive gene expression levels of a group of test subjects having no lung cancer, both of which are in a training cohort, as a data set, the degree of difference in the expression level of each gene between the two groups is obtained by use of, for example, the P value of a parametric analysis such as t-test, the P value of a nonparametric analysis such as the Mann-Whitney's U test or the P value of the Wilcoxon test.

(920) The gene can be regarded as being statistically significant when the critical rate (significance level) as the P value obtained by the test is smaller than, for example, 5%, 1%, or 0.01%.

(921) In order to correct an increased probability of type I error attributed to the repetition of a test, a method known in the art, for example, Bonferroni or Holm method, can be used for the correction (e.g., Yasushi Nagata et al., “Basics of statistical multiple comparison methods”, Scientist Press Co., Ltd. (Tokyo, Japan) (2007)). As an example of the Bonferroni correction, for example, the P value obtained by a test is multiplied by the number of repetitions of the test, i.e., the number of genes used in the analysis, and the obtained value can be compared with a desired significance level to suppress a probability of causing type I error in the whole test.

(922) Instead of statistical tests, the absolute value of an expression ratio of a median value of each gene expression level (fold change) between gene expression levels of a group of patients having lung cancer and gene expression levels of a group of test subjects having no lung cancer may be calculated to select a gene that is used for an explanatory variable in a discriminant. Alternatively, ROC curves may be prepared using gene expression levels of a group of patients having lung cancer and a group of test subjects having no lung cancer, and a gene that is used for an explanatory variable in a discriminant can be selected on the basis of an AUROC value.

(923) Next, a discriminant that can be calculated by various methods described above is prepared using any number of genes having large difference in their gene expression levels determined here. Examples of the method for constructing a discriminant that produces the largest discrimination accuracy include a method of constructing a discriminant in every combination of genes that satisfy the significance level being P value, and a method of repetitively evaluating the genes for use in the preparation of a discriminant while increasing the number of genes one by one in a descending order of difference in gene expression level (Furey T S. et al., 2000, Bioinformatics., Vol. 16, p. 906-14). To the discriminant, the gene expression level of another independent patient having a lung cancer or a test subject having no lung cancer is assigned as an explanatory variable to calculate discrimination results of the group to which the independent patient having a lung cancer or the test subject having no lung cancer belongs. Specifically, the gene set for diagnosis found and the discriminant constructed using the gene set for diagnosis can be evaluated in an independent sample cohort to find more universal gene set for diagnosis that can detect a lung cancer and a more universal method for discriminating a lung cancer.

(924) In preparing a discriminant using expression levels of multiple genes as an explanatory variable, it is not necessary to select a gene having a clear difference in expression level between the group of lung cancer patients and the group of test subjects having no lung cancer as described above. Specifically, if expression levels of multiple genes are used in combination even though the expression levels of individual genes do not clearly differ, a discriminant having high discriminant performance can be obtained, as the case may be. Because of this, a method of directly searching a discriminant having high discriminant performance without prior selection of the gene to be employed in the discriminant can also be used.

(925) Split-sample method is preferably used for evaluating the performance (generality) of the discriminant. Specifically, a data set is divided into a training cohort and a validation cohort, and gene selection by a statistical test and discriminant preparation are performed using the training cohort. Accuracy, sensitivity, and specificity are calculated using a result of discriminating a validation cohort according to the discriminant, and a true group to which the validation cohort belongs, to evaluate the performance of the discriminant. On the other hand, instead of dividing a data set, the gene selection by a statistical test and discriminant preparation may be performed using all of samples, and accuracy, sensitivity, and specificity can be calculated by the discriminant using a newly prepared sample cohort for evaluation of the performance of the discriminant.

(926) The present invention provides a polynucleotide(s) for detection or diagnosis of a disease useful for diagnosing and treating a lung cancer, a method for detecting a lung cancer using the polynucleotide(s), and a kit and device for detecting or diagnosing a lung cancer, comprising the polynucleotide(s). Particularly, in order to select a gene(s) for diagnosis and prepare a discriminant so as to exhibit accuracy beyond the lung cancer diagnosis method using the existing tumor marker CEA, a gene set for diagnosis and a discriminant for the method of present invention can be constructed, which exhibit accuracy beyond CEA, for example, by comparing expressed genes in serum from a patient confirmed to be negative using CEA but finally found to have a lung cancer by detailed examination such as computed tomography using a contrast medium, with genes expressed in serum from a patient having no lung cancer.

(927) For example, the gene set for diagnosis is set to any combination selected from: one or two or more of the polynucleotides based on a nucleotide sequence(s) represented by any of SEQ ID NOs: 1 to 163 as described above; and optionally one or two or more of the polynucleotides based on a nucleotide sequence(s) represented by any of SEQ ID NOs: 164 to 329. Further, a discriminant is constructed using the expression levels of the gene set for diagnosis in samples from a lung cancer patient as a result of tissue diagnosis and samples from a test subject having no lung cancer as a result of tissue diagnosis. As a result, whether a subject, from which a sample with unknown lung cancer status is provided, has a lung cancer or not can be determined with 100% accuracy at the maximum by measuring expression levels of the gene set for diagnosis in the sample.

EXAMPLES

(928) The present invention will be described further specifically with reference to Examples below. However, the scope of the present invention is not intended to be limited by these Examples.

Reference Example

(929) <Collection of Samples>

(930) Sera were collected using VENOJECT II vacuum blood collecting tube VP-AS109K60 (Terumo Corp. (Japan)) from total 10,869 people (Table 11a) including 4,660 healthy subjects, 327 benign bone and soft tissue tumor patients, 41 benign breast disease patients, 1,694 lung cancer patients, 1,417 stomach cancer patients, 595 esophagus cancer patients, 355 liver cancer patients, 862 pancreatic cancer patients, 406 biliary cancer patients, and 512 bladder cancer patients, after receiving their informed consents. The histological types of the lung cancer patients were adenocarcinoma in 1,308 people, squamous cell carcinoma in 243 people, large cell carcinoma in 23 people, small cell carcinoma in 25 people, adenosquamous carcinoma in 18 people, polymorphic cell cancer in 33 people, salivary gland-type cancer in 2 people, carcinoid tumor in 13 people, preinvasive lesion in 1 person, and other lung cancers in 28 people. Also, the stages of the lung cancer patients were stage IA in 1,068 people, stage IB in 337 people, stage IIA in 97 people, stage IIB in 89 people, stage IIIA in 46 people, stage IIIB in 29 people, stage IV in 4 people, unknown stages in 24 people (Table 2).

(931) <Extraction of Total RNA>

(932) Total RNA was obtained using a reagent for “RNA extraction in 3D-Gene™ RNA extraction reagent from liquid sample kit” (Toray Industries, Inc. (Japan)) according to the protocol provided by the manufacturer, from 300 μL of the serum sample obtained from each of 10,869 people in total.

(933) <Measurement of Gene Expression Level>

(934) MicroRNA in the total RNA that was obtained from the serum samples of a total of 10,869 people was fluorescently labeled by use of 3D-Gene™ miRNA Labeling kit (Toray Industries, Inc.) according to the protocol provided by the manufacturer. The oligo DNA chip used was 3D-Gene™ Human miRNA Oligo chip (Toray Industries, Inc.) with attached probes having sequences complementary to 2,565 miRNAs among the miRNAs registered in miRBase Release 21. Hybridization under stringent conditions and washing following the hybridization were performed according to the protocol provided by the manufacturer. The DNA chip was scanned using 3D-Gene™ scanner (Toray Industries, Inc.) to obtain images. Fluorescence intensity was digitized using 3D-Gene™ Extraction (Toray Industries, Inc.). The digitized fluorescence intensity was converted to a logarithmic value having a base of 2 and used as a gene expression level, from which a blank value was subtracted. A missing value was replaced with a signal value 0.1. As a result, the comprehensive gene expression levels of the miRNAs in the sera were obtained for the 10,869 people described above.

(935) Subsequently, the samples were extracted for use in the discriminant analysis of lung cancer. In the description below, healthy subjects, benign bone and soft tissue tumor patients and benign breast disease patients, and patients having a cancer other than lung cancer will be collectively referred to as “test subjects without lung cancer”. Also, stomach cancer, esophagus cancer, liver cancer, pancreatic cancer, biliary cancer and bladder cancer patients will be collectively referred to as “patients having a cancer other than lung cancer”. Firstly, 1,694 lung cancer patients were used as a positive sample group. Secondly, 1,800 people from the healthy subjects described above, and a total of 1,800 people including 300 people having each cancer other than lung cancer were extracted at random, and combined with 368 benign bone and soft tissue tumor patients and benign breast disease patients to select a total of 3,968 people as a negative sample group (Table 11b). Thirdly, 70% of each sample group was used as a training cohort and the remaining 30% thereof as a validation cohort. Specifically, the training cohort consisted of 1,233 healthy subjects, 263 benign bone and soft tissue tumor patients and benign breast disease patients, 1,186 lung cancer patients and 1,281 patients having a cancer other than lung cancer; while the validation cohort consisted of 567 healthy subjects, 105 benign bone and soft tissue tumor patients and benign breast disease patients, 508 lung cancer patients and 519 patients having a cancer other than lung cancer. Calculation and statistical analysis using the digitized gene expression levels of the miRNAs were carried out using R language 3.3.1 (R Core Team (2016). R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. URL https://www.R-project.org/.) and MASS package 7.3.45 (Venables, W. N. & Ripley, B. D. (2002) Modern Applied Statistics with S. Fourth Edition. Springer, New York. ISBN 0-387-95457-0).

(936) TABLE-US-00002 TABLE 2 Stage IA IB IIA IIB IIIA IIIB IV Unknown Total Histological Adenocarcinoma 917 250 57 36 19 20 2 7 1308 type Squamous cell 95 54 30 39 18 6 0 1 243 carcinoma Large cell carcinoma 11 5 2 2 2 0 0 1 23 Small cell carcinoma 7 2 1 0 0 0 0 1 11 Combined small 8 3 2 0 0 0 1 0 14 cell carcinoma Adenosquamous 10 5 0 3 0 0 0 0 18 carcinoma Polymorphic cell 6 11 4 6 4 0 1 1 33 cancer Salivary gland-type 0 0 0 0 0 1 0 1 2 cancer Carcinoid tumor 3 1 0 0 1 0 0 8 13 Preinvasive lesion 1 0 0 0 0 0 0 0 1 Others 10 6 1 3 2 2 0 4 28 Total 1068 337 97 89 46 29 4 24 1694

(937) TABLE-US-00003 TABLE 11 b. b1. b2. All Training Validation samples cohort cohort a. used in used in used in All discriminant discriminant discriminant Subject samples analysis analysis analysis Healthy 4660 1800 1233 567 Benign bone and 327 368 263 105 soft tissue tumor Benign breast 41 disease Lung cancer 1694 1694 1186 508 Stomach cancer 1417 1800 1281 519 Esophagus cancer 595 Liver cancer 355 Pancreatic cancer 862 Biliary cancer 406 Bladder cancer 512

Example 1

(938) <Discriminant Analysis Using Up to Two miRNAs in Combination>

(939) In this Example, a discriminant(s) was prepared using one or two gene markers in the training cohort including the lung cancer patients and the test subjects without lung cancer (Table 11 b1), and then, the discriminant performance was evaluated in the validation cohort (Table 11b2). Based on the evaluation, gene(s) used in discriminant(s) with high performance were extracted to obtain gene marker(s) that was able to detect lung cancer.

(940) To be more specific, firstly the miRNA expression levels of the training cohort and the validation cohort obtained in the preceding Reference Examples were combined and normalized by global normalization. Secondly, in order to acquire diagnostic markers with higher reliability, only 396 genes having the expression level of 2.sup.6 or higher in 50% or more of the samples in either of the group of the lung cancer patients or the group of the test subjects without lung cancer were selected as analytes.

(941) Thirdly, one and two in combination of the 396 gene expression level measurement values described above were subjected to the Fisher's discriminant analysis to construct discriminants to discriminate the presence or absence of lung cancer. Accuracy, sensitivity, and specificity in the validation cohort were further calculated using the discriminants prepared above and the discriminant performance was validated using the independent samples. As a result, 645 discriminants with 80% or more discrimination accuracy in the validation cohort were obtained. Among these discriminants, for the discriminants that used a combination of two gene expression levels, only those whose discrimination accuracy is better than the discriminant that used any single one of the gene expression levels were selected, which led to 490 discriminants with 80% or more discrimination accuracy. The 281 genes used in these discriminants were selected as diagnostic markers for the lung cancer patients and the test subjects without lung cancer. In this way, miR-6787-5p, miR-920, miR-3622a-5p, miR-1185-1-3p, miR-4327, miR-5739, miR-937-5p, miR-1181, miR-1185-2-3p, miR-1193, miR-1207-5p, miR-1238-5p, miR-1246, miR-1249-5p, miR-1292-3p, miR-1469, miR-1470, miR-197-5p, miR-208a-5p, miR-2110, miR-211-3p, miR-2467-3p, miR-3122, miR-3141, miR-3156-5p, miR-3158-5p, miR-3160-5p, miR-3180-3p, miR-3191-3p, miR-3194-3p, miR-320b, miR-328-5p, miR-3610, miR-3619-3p, miR-3620-5p, miR-370-3p, miR-373-5p, miR-3917, miR-3937, miR-4259, miR-4281, miR-4294, miR-4419b, miR-4428, miR-4429, miR-4433a-3p, miR-4447, miR-4449, miR-4459, miR-4480, miR-4485-5p, miR-4486, miR-4488, miR-4489, miR-4505, miR-4513, miR-4515, miR-4530, miR-4535, miR-4635, miR-4640-5p, miR-4646-5p, miR-4656, miR-4663, miR-4665-5p, miR-4706, miR-4707-5p, miR-4708-3p, miR-4710, miR-4718, miR-4722-5p, miR-4727-3p, miR-4730, miR-4734, miR-4740-5p, miR-4747-3p, miR-4749-5p, miR-4755-3p, miR-4763-5p, miR-4787-3p, miR-5008-5p, miR-5010-5p, miR-504-3p, miR-5090, miR-5100, miR-5196-5p, miR-551b-5p, miR-557, miR-5787, miR-6090, miR-6124, miR-6132, miR-6510-5p, miR-6511b-5p, miR-6515-3p, miR-654-5p, miR-658, miR-668-5p, miR-6722-5p, miR-6724-5p, miR-6729-3p, miR-6737-5p, miR-6756-5p, miR-6762-5p, miR-6763-3p, miR-6766-5p, miR-6769a-5p, miR-6771-5p, miR-6786-5p, miR-6789-5p, miR-6794-5p, miR-6796-3p, miR-6797-5p, miR-6800-3p, miR-6802-5p, miR-6803-5p, miR-6805-3p, miR-6805-5p, miR-6807-5p, miR-6812-5p, miR-6819-5p, miR-6822-5p, miR-6824-5p, miR-6826-5p, miR-6850-5p, miR-6858-5p, miR-6861-5p, miR-6880-3p, miR-7107-5p, miR-7109-5p, miR-7114-5p, miR-7704, miR-7846-3p, miR-8052, miR-8060, miR-8071, miR-8073, miR-874-5p, miR-1343-3p, miR-6746-5p, miR-422a, miR-187-5p, miR-4632-5p, miR-6791-5p, miR-103a-3p, miR-107, miR-1199-5p, miR-1225-3p, miR-1225-5p, miR-1228-5p, miR-1229-5p, miR-1233-5p, miR-1237-5p, miR-1247-3p, miR-1249-3p, miR-1254, miR-1260b, miR-1268a, miR-1268b, miR-1273g-3p, miR-128-1-5p, miR-128-2-5p, miR-1290, miR-150-3p, miR-17-3p, miR-1908-5p, miR-1909-3p, miR-1914-3p, miR-1915-3p, miR-191-5p, miR-22-3p, miR-23b-3p, miR-24-3p, miR-296-3p, miR-296-5p, miR-3131, miR-3162-5p, miR-3188, miR-3196, miR-3197, miR-320a, miR-342-5p, miR-3621, miR-3648, miR-3656, miR-365a-5p, miR-3665, miR-3679-5p, miR-371a-5p, miR-3940-5p, miR-423-5p, miR-4257, miR-4270, miR-4271, miR-4286, miR-4298, miR-4417, miR-4442, miR-4446-3p, miR-4448, miR-4454, miR-4467, miR-4472, miR-4507, miR-4516, miR-451a, miR-4649-5p, miR-4651, miR-4665-3p, miR-4674, miR-4675, miR-4689, miR-4695-5p, miR-4697-5p, miR-4725-3p, miR-4739, miR-4745-5p, miR-4763-3p, miR-4792, miR-486-3p, miR-5001-5p, miR-5195-3p, miR-550a-5p, miR-5698, miR-6075, miR-6088, miR-6089, miR-6125, miR-6126, miR-614, miR-615-5p, miR-619-5p, miR-638, miR-642b-3p, miR-650, miR-663a, miR-663b, miR-6717-5p, miR-6721-5p, miR-6726-5p, miR-6727-5p, miR-6738-5p, miR-6741-5p, miR-6749-5p, miR-6752-5p, miR-675-5p, miR-6757-5p, miR-6763-5p, miR-6765-5p, miR-6775-5p, miR-6780b-5p, miR-6782-5p, miR-6784-5p, miR-6800-5p, miR-6806-5p, miR-6840-3p, miR-6848-5p, miR-6851-5p, miR-6870-5p, miR-6872-3p, miR-6875-5p, miR-6877-5p, miR-6879-5p, miR-6880-5p, miR-6885-5p, miR-6887-5p, miR-7108-5p, miR-711, miR-7113-3p, miR-744-5p, miR-760, miR-7845-5p, miR-7847-3p, miR-7977, miR-8059, miR-8063, miR-8072, miR-874-3p, miR-92a-2-5p, miR-92b-5p, and miR-940, and the relevant polynucleotides consisting of nucleotide sequences of SEQ ID NOs: 1 to 138 and 164 to 306, were found. Among them, the genes newly found as the markers for examining the presence or absence of lung cancer are polynucleotides consisting of the nucleotide sequences represented by SEQ ID NOs: 1 to 138.

(942) The sensitivities in the validation cohort determined by the discriminants obtained using any single one of the polynucleotides consisting of the nucleotide sequences represented by SEQ ID NOs: 188, 164, 85, 13, 175, 137, 231, 195, 263, 165, 226, 94, 45, 190, 274, 80, 220, 198, 98, 43, 2, 115, 299, 50, 196, 31, 182, 72, 96, 70, 40, 127, 183, 68, 3, 60, 66, 25, 75, 12, 255, 7, 1, 291, 87, 199, 120, 222, 278, 260, 246, 197, 103, 22, 106, 57, 29, 184, 206, 135, 179, 287, 56, 207, 261, 201, 217, 172, 300, 102, 285, 20, 21, 73, 78, 15, 30, 134, 76, 107, 97, 23, 33, 215, 122, 38, 54, 225, 26, 298, 114, 185, 128, 109, 104, 277, 303, 181, 59, 209, 236, 214, 51, 99, 105, 294, 58, 272, 101, 42, 180, 170, 47, 44, 16, 124, 241, 46, 130, 79, 247, 262, 95, 267, 69, 259, 118, 234, 138, 286, 110, 173, 200, 257, 167, 8, 111, 27, 64, 304, 177, 74, 34, 17, 36, 171, 251, 211, 193, and 256 among the polynucleotides described above, are shown in Table 3. Also, discriminant coefficients and constant terms are shown in Table 4. In this context, the general sensitivity of the existing marker CEA has been reported as being 69%. Accordingly, it was demonstrated that the polynucleotides represented by these SEQ ID NOs singly detect lung cancer with sensitivity beyond CEA.

(943) Discriminants that were all able to discriminate lung cancer with 80% or more accuracy were also able to be prepared by combining each of the expression levels of the 281 genes represented by the nucleotide sequences of SEQ ID NOs: 1 to 138 and 164 to 306 with another gene expression level (Table 5). In this respect, discriminant coefficients and constant terms are shown in Table 6. The performance of all the discriminants using these combinations exceeded the discriminant performance of the existing marker CEA. Note that, in the tables, in the column of “SEQ ID NO or Gene”, the combinations of multiple polynucleotides used are described by SEQ ID NOs. (the same applies to tables described later).

(944) From the above, it was demonstrated that all polynucleotides consisting of the nucleotide sequences represented by SEQ ID NOs: 1 to 138 and 164 to 306 are genes capable of discriminating a lung cancer patient from a test subject without lung cancer with high accuracy if these are used alone or in combination of two or more.

(945) TABLE-US-00004 TABLE 3 SEQ Training cohort Validation cohort ID Accu- Sensi- Speci- Accu- Sensi- Speci- NO: racy tivity ficity racy tivity ficity 188 71.9 98.1 60.8 72.7 97.0 62.3 164 83.4 97.0 77.7 83.8 95.9 78.6 85 73.2 95.3 63.8 74.0 94.3 65.4 13 73.4 93.4 64.9 73.0 91.7 65.1 175 71.3 91.4 62.7 71.5 91.5 62.9 137 74.9 93.9 66.8 74.4 91.1 67.3 231 74.4 91.8 66.9 75.8 90.2 69.6 319 72.2 92.6 63.5 72.7 90.2 65.2 195 71.1 92.2 62.0 71.9 90.2 64.1 263 71.5 91.0 63.2 73.0 90.0 65.7 165 78.4 89.7 73.6 79.7 89.8 75.4 226 72.0 89.5 64.5 74.5 89.6 68.0 94 77.3 87.6 72.9 77.3 88.8 72.5 45 73.3 88.9 66.6 75.0 88.8 69.1 190 68.7 89.0 60.0 70.3 88.4 62.6 274 74.2 85.7 69.2 75.0 88.2 69.4 328 72.1 89.4 64.7 74.4 87.2 68.9 80 68.9 86.8 61.2 70.6 87.0 63.6 220 74.1 87.9 68.2 75.5 86.8 70.7 198 73.1 87.5 67.0 73.7 86.6 68.2 98 76.2 86.6 71.7 77.6 86.4 73.8 43 72.0 84.2 66.7 73.7 86.4 68.3 316 69.2 86.0 62.1 71.5 86.4 65.2 2 79.7 87.4 76.4 78.3 86.2 75.0 115 73.4 88.0 67.2 74.5 86.0 69.5 299 71.7 88.0 64.7 73.2 85.8 67.8 50 70.4 87.4 63.2 70.9 85.8 64.6 150 71.6 88.5 64.4 71.0 85.6 64.8 196 73.0 86.9 67.1 72.8 85.2 67.5 31 64.1 83.6 55.7 67.3 85.2 59.7 182 70.0 86.0 63.2 71.8 85.0 66.2 72 74.0 87.0 68.5 75.5 84.8 71.5 318 67.8 84.7 60.5 69.3 84.8 62.6 149 75.5 85.8 71.2 75.0 84.6 70.9 312 73.1 87.4 67.0 73.8 84.6 69.2 96 71.4 84.3 65.9 72.7 84.3 67.8 329 73.7 84.1 69.3 74.7 84.1 70.7 70 71.4 86.5 64.9 72.1 84.1 67.0 40 76.4 88.7 71.2 76.4 83.7 73.3 127 68.7 84.5 62.0 71.3 83.3 66.2 153 76.4 86.1 72.3 76.8 83.1 74.1 183 72.9 81.8 69.1 73.9 83.1 69.9 148 70.6 83.5 65.1 71.7 83.1 66.9 68 73.3 86.4 67.7 73.3 82.9 69.2 3 79.2 85.7 76.4 79.7 82.7 78.4 60 77.8 84.4 75.0 78.2 82.5 76.4 66 74.8 85.5 70.2 76.3 82.5 73.7 25 66.3 81.6 59.8 68.6 82.5 62.6 75 70.7 83.8 65.1 71.8 82.3 67.3 12 69.2 84.7 62.6 70.5 82.3 65.4 255 68.9 86.3 61.5 69.6 82.3 64.2 7 75.4 81.6 72.8 76.7 82.1 74.4 1 79.4 84.7 77.1 79.4 81.9 78.3 291 73.3 81.6 69.7 73.9 81.9 70.4 162 64.6 81.5 57.4 66.3 81.9 59.6 163 75.3 83.0 72.1 74.7 81.7 71.8 87 72.6 84.2 67.6 73.3 81.7 69.7 199 68.4 81.3 62.9 70.9 81.7 66.2 120 73.7 80.9 70.6 73.3 81.5 69.9 222 70.2 77.2 67.3 71.3 81.5 67.0 311 74.5 82.6 71.0 75.2 81.3 72.5 278 64.5 83.7 56.4 65.7 81.3 59.1 260 76.7 84.3 73.4 76.5 81.1 74.6 246 71.6 85.2 65.8 72.1 81.1 68.3 197 73.7 84.1 69.3 73.9 80.9 70.9 103 68.4 80.9 63.1 70.1 80.9 65.5 22 70.3 82.6 65.1 71.4 80.7 67.4 106 70.9 83.2 65.7 71.6 80.5 67.8 322 69.4 81.3 64.3 71.5 80.5 67.7 57 69.1 83.5 63.0 70.9 80.5 66.8 309 68.2 80.9 62.7 69.6 80.5 64.9 29 78.1 82.6 76.2 78.2 80.1 77.4 184 71.5 78.2 68.6 72.2 80.1 68.8 206 63.7 81.3 56.2 65.0 80.1 58.5 135 78.9 83.3 77.0 77.9 79.9 77.1 179 73.5 81.5 70.0 75.0 79.9 72.9 287 75.9 82.5 73.1 77.1 79.5 76.1 56 71.9 79.9 68.5 73.9 79.5 71.5 207 67.0 81.8 60.7 68.9 79.5 64.3 261 64.4 78.8 58.3 66.2 79.5 60.5 201 71.8 80.4 68.1 71.6 79.1 68.3 217 74.7 80.6 72.2 76.3 78.9 75.1 317 71.9 79.0 68.9 72.7 78.9 70.0 172 69.4 78.4 65.6 71.3 78.9 68.1 300 69.6 82.7 64.1 70.7 78.7 67.3 102 77.1 78.6 76.5 76.0 78.5 75.0 285 69.5 81.0 64.6 69.9 78.5 66.2 20 73.8 80.1 71.2 74.3 78.3 72.5 159 70.9 80.7 66.8 70.6 78.3 67.3 21 68.4 80.2 63.4 70.5 78.1 67.2 73 61.6 79.0 54.2 64.0 78.1 57.9 78 70.5 80.9 66.1 70.9 78.0 67.8 15 68.6 76.5 65.2 70.5 78.0 67.3 30 70.3 79.8 66.3 71.3 77.8 68.5 134 70.6 78.7 67.2 72.9 77.6 70.9 315 67.4 73.5 64.8 70.6 77.6 67.6 76 66.5 76.5 62.2 67.3 77.6 63.0 107 71.3 80.2 67.5 72.5 77.2 70.4 97 61.8 75.8 55.8 63.0 77.0 57.0 23 74.8 81.2 72.0 74.7 76.8 73.9 33 71.7 78.5 68.7 72.0 76.4 70.2 307 67.9 76.0 64.4 69.7 76.2 67.0 215 63.0 78.6 56.4 64.4 76.2 59.4 122 71.9 79.0 68.8 71.3 76.0 69.4 38 66.4 77.9 61.5 68.1 76.0 64.7 54 71.4 78.5 68.3 70.8 75.8 68.7 225 71.0 78.1 68.0 70.6 75.6 68.5 26 65.7 76.6 61.0 65.8 75.6 61.6 298 66.3 76.8 61.8 66.5 75.4 62.6 114 64.7 74.2 60.6 66.3 75.4 62.4 185 69.0 76.4 65.8 70.6 75.2 68.6 128 68.6 77.7 64.7 69.6 75.2 67.2 109 68.2 75.0 65.3 69.4 75.2 66.9 104 67.4 71.8 65.6 66.0 75.2 62.1 277 65.8 74.5 62.2 64.6 75.2 60.0 327 65.0 76.4 60.1 64.6 75.2 60.0 303 68.3 76.1 65.0 68.9 75.0 66.3 181 69.1 76.3 66.0 69.8 74.8 67.7 59 66.8 74.9 63.4 67.7 74.8 64.7 209 63.2 73.2 58.9 65.3 74.8 61.2 236 61.7 76.1 55.6 63.2 74.8 58.3 214 66.6 74.7 63.2 67.9 74.4 65.1 51 65.1 76.6 60.1 65.0 74.2 61.0 140 65.9 75.5 61.8 64.7 74.2 60.7 99 69.2 75.5 66.5 69.1 74.0 67.0 105 66.8 75.6 63.0 67.3 74.0 64.4 294 63.2 74.6 58.4 64.4 74.0 60.4 58 59.4 75.0 52.8 59.7 73.8 53.7 143 70.1 75.9 67.6 71.2 73.6 70.2 272 65.6 78.1 60.2 65.8 73.6 62.5 101 65.1 74.5 61.1 65.7 73.4 62.4 144 68.3 75.4 65.3 68.2 73.0 66.1 42 68.3 77.5 64.4 67.6 73.0 65.3 180 68.3 76.6 64.8 67.7 72.8 65.5 170 72.0 74.7 70.9 72.7 72.6 72.7 47 68.5 71.0 67.4 69.7 72.6 68.4 44 68.7 77.6 64.9 68.5 72.6 66.8 16 65.2 71.8 62.4 67.8 72.4 65.8 124 65.1 74.7 61.0 66.5 72.4 63.9 241 64.8 72.1 61.7 66.0 72.4 63.3 46 68.2 73.0 66.2 67.4 72.2 65.3 321 65.7 75.6 61.4 66.5 72.2 64.1 130 69.1 72.4 67.7 69.9 72.0 68.9 79 64.3 71.8 61.1 66.3 72.0 63.8 247 62.1 71.2 58.2 64.4 72.0 61.2 262 65.3 70.0 63.2 68.0 71.7 66.4 95 66.6 72.4 64.1 67.0 71.7 65.0 142 65.5 71.2 63.0 65.0 71.7 62.1 267 64.0 73.4 60.0 64.3 71.7 61.2 69 67.8 71.4 66.2 68.9 71.5 67.8 259 62.7 69.6 59.8 65.5 71.5 63.0 118 65.4 72.6 62.3 67.2 71.3 65.4 234 65.5 71.1 63.1 65.0 71.3 62.3 138 65.3 71.8 62.5 64.0 71.3 60.9 286 69.0 68.8 69.1 69.7 71.1 69.1 110 67.2 68.0 66.9 69.1 71.1 68.3 173 70.2 78.0 66.9 68.6 71.1 67.6 320 65.1 69.9 63.1 65.9 71.1 63.6 200 64.6 72.3 61.3 64.9 71.1 62.2 257 67.4 69.6 66.5 69.6 70.9 69.1 167 67.1 72.7 64.7 66.9 70.9 65.2 314 68.0 74.3 65.3 65.4 70.9 63.1 8 62.7 76.5 56.8 60.0 70.9 55.3 111 78.3 74.3 80.0 76.2 70.7 78.5 27 68.2 72.8 66.2 69.2 70.5 68.7 64 68.0 75.0 65.0 68.5 70.1 67.8 304 64.1 69.5 61.9 65.1 70.1 63.0 177 59.3 67.5 55.9 63.5 70.1 60.7 74 68.2 67.5 68.6 70.9 69.7 71.4 34 66.3 69.8 64.8 66.9 69.7 65.7 17 66.3 72.9 63.4 65.1 69.7 63.1 36 64.3 73.6 60.4 64.4 69.7 62.1 171 72.0 73.4 71.3 72.3 69.5 73.6 251 62.8 70.9 59.3 64.0 69.5 61.7 211 65.2 71.9 62.3 65.5 69.3 63.9 193 69.5 71.7 68.6 69.7 69.1 69.9 256 62.4 69.0 59.6 65.2 69.1 63.6

(946) TABLE-US-00005 TABLE 4 SEQ ID NO: Coefficient Constant term 188 0.46 −3.96 164 1.52 −12.87 85 0.76 −9.89 13 0.44 −3.44 175 −2.56 28.63 137 1.19 −9.35 231 0.52 −3.92 319 0.50 −5.37 195 0.52 −2.98 263 0.74 −5.56 165 1.72 −13.28 226 0.90 −9.97 94 1.04 −6.31 45 1.09 −7.88 190 0.52 −2.78 274 −3.35 34.66 328 0.90 −8.02 80 1.00 −7.29 220 1.16 −8.43 198 0.71 −4.51 98 0.90 −4.61 43 1.05 −7.31 316 1.29 −8.88 2 1.01 −6.10 115 2.20 −20.21 299 1.00 −9.37 50 0.47 −2.72 150 0.56 −3.02 196 0.56 −3.19 31 0.53 −3.07 182 1.11 −10.40 72 0.75 −4.45 318 0.74 −5.73 149 0.81 −5.37 312 0.61 −2.91 96 0.70 −3.37 329 0.81 −5.51 70 0.53 −4.19 40 0.86 −4.96 127 1.53 −12.09 153 0.76 −4.05 183 −3.32 35.60 148 1.25 −8.23 68 0.68 −5.43 3 1.39 −9.03 60 0.86 −4.09 66 1.97 −16.60 25 0.56 −3.00 75 0.61 −3.65 12 0.98 −7.25 255 0.72 −7.17 7 2.37 −19.98 1 2.02 −19.02 291 1.25 −8.99 162 0.63 −3.74 163 0.81 −4.70 87 0.73 −3.97 199 0.90 −6.60 120 1.00 −6.11 222 3.07 −26.17 311 0.59 −3.50 278 −1.45 16.91 260 0.90 −4.36 246 1.85 −16.38 197 0.57 −3.42 103 2.01 −17.60 22 0.53 −4.56 106 1.05 −6.86 322 0.95 −7.58 57 0.56 −3.59 309 0.71 −5.45 29 1.18 −6.74 184 −3.26 31.56 206 0.66 −4.32 135 0.89 −4.22 179 1.56 −11.11 287 1.88 −15.11 56 1.31 −8.81 207 0.63 −3.95 261 1.04 −12.53 201 1.27 −10.31 217 1.58 −12.07 317 2.32 −21.17 172 0.85 −5.07 300 0.91 −9.12 102 1.40 −9.99 285 0.94 −5.62 20 1.03 −6.33 159 1.19 −7.36 21 1.16 −8.70 73 −0.53 4.41 78 0.48 −2.44 15 0.87 −5.39 30 0.43 −3.27 134 1.00 −6.04 315 0.74 −9.76 76 0.75 −4.45 107 1.18 −8.80 97 0.57 −3.71 23 0.91 −4.91 33 0.86 −4.72 307 1.66 −11.62 215 −1.63 18.47 122 0.80 −4.37 38 0.83 −5.46 54 0.67 −3.37 225 0.63 −5.27 26 0.52 −3.11 298 0.87 −6.15 114 0.64 −3.71 185 0.81 −6.70 128 1.01 −6.33 109 −2.71 33.33 104 1.28 −10.29 277 0.63 −3.80 327 0.52 −3.47 303 0.78 −4.47 181 0.87 −5.65 59 0.67 −3.76 209 1.09 −14.30 236 0.88 −7.04 214 1.28 −9.55 51 0.64 −3.99 140 0.81 −5.16 99 0.73 −3.95 105 0.77 −4.44 294 0.62 −3.83 58 −1.09 10.55 143 0.62 −3.40 272 0.96 −7.96 101 0.93 −5.82 144 0.67 −3.81 42 −1.55 15.71 180 1.31 −9.04 170 0.57 −2.49 47 1.03 −7.03 44 0.64 −3.54 16 1.18 −13.90 124 0.97 −7.04 241 −2.20 24.78 46 1.29 −9.94 321 1.00 −7.64 130 1.67 −13.02 79 0.65 −3.61 247 0.69 −4.92 262 0.84 −7.44 95 1.45 −10.46 142 0.65 −3.63 267 0.69 −4.79 69 0.55 −4.42 259 0.64 −6.21 118 −1.78 19.05 234 0.72 −4.36 138 0.57 −3.21 286 −1.05 8.89 110 1.63 −16.52 173 1.60 −11.35 320 0.62 −3.53 200 1.40 −10.95 257 0.51 −3.87 167 1.29 −11.15 314 1.59 −12.95 8 0.66 −4.07 111 2.44 −20.94 27 0.38 −2.72 64 0.45 −2.24 304 −0.61 4.99 177 0.59 −7.14 74 0.86 −10.97 34 0.84 −6.99 17 0.77 −4.63 36 0.69 −4.14 171 0.57 −2.50 251 0.85 −9.59 211 1.02 −7.34 193 1.57 −12.18 256 0.47 −3.00

(947) TABLE-US-00006 TABLE 5 Training cohort Validation cohort Accu- Sensi- Speci- Accu- Sensi- Speci- Gene racy tivity ficity racy tivity ficity 18_164 86.4 98.0 81.4 86.7 98.2 81.8 255_164 86.9 96.1 83.0 86.6 96.1 82.5 177_164 86.1 94.6 82.5 86.3 94.5 82.9 4_164 85.8 91.1 83.5 86.0 91.3 83.7 164_9 85.4 92.0 82.6 85.9 91.5 83.5 300_164 85.8 96.1 81.5 85.7 96.1 81.3 272_164 84.8 97.6 79.4 85.7 97.0 80.9 206_164 86.0 95.3 82.0 85.6 93.9 82.0 12_164 85.6 96.0 81.2 85.6 95.5 81.4 166_164 85.6 92.8 82.5 85.6 91.7 83.0 168_164 85.3 97.6 80.1 85.6 97.4 80.6 6_164 85.0 97.1 79.8 85.6 97.0 80.8 259_164 85.0 94.7 80.8 85.5 93.9 81.9 115_164 84.8 96.4 79.8 85.5 96.1 81.0 164_129 84.5 95.8 79.7 85.4 95.3 81.2 190_164 85.5 95.4 81.3 85.3 95.1 81.2 199_164 85.4 95.9 81.0 85.3 95.9 80.8 66_164 85.4 96.3 80.7 85.3 96.5 80.5 164_107 85.4 97.1 80.4 85.3 97.2 80.3 207_164 85.3 96.8 80.4 85.3 95.3 81.0 263_164 85.1 97.5 79.8 85.3 97.0 80.4 16_164 85.0 95.3 80.6 85.3 95.1 81.2 37_164 84.9 94.9 80.6 85.3 94.1 81.5 38_164 84.9 96.9 79.8 85.3 96.3 80.7 261_164 85.5 94.8 81.6 85.2 93.9 81.5 305_164 85.2 94.7 81.2 85.2 93.7 81.6 55_164 85.1 94.2 81.2 85.2 93.1 81.9 127_164 84.6 95.6 79.9 85.2 95.1 80.9 104_164 84.2 96.2 79.1 85.2 96.1 80.5 31_164 85.2 95.9 80.6 85.1 94.3 81.2 121_164 84.7 97.8 79.0 85.1 97.4 79.8 81_164 84.6 95.4 79.9 85.1 95.5 80.7 295_164 84.6 93.8 80.7 85.1 93.1 81.6 6_165 84.5 95.3 79.9 85.1 95.9 80.5 25_164 84.5 96.1 79.5 85.1 95.5 80.6 83_164 84.4 97.1 79.0 85.1 96.7 80.2 32_164 85.1 94.7 81.0 85.0 94.1 81.1 247_164 84.5 95.8 79.7 85.0 95.1 80.7 26_164 84.1 96.2 78.9 85.0 96.3 80.2 302_164 84.5 95.4 79.8 84.9 94.7 80.7 268_164 84.5 97.3 79.0 84.9 96.9 79.8 90_164 84.4 95.8 79.5 84.9 95.9 80.2 287_164 84.2 96.9 78.8 84.9 96.7 79.9 278_164 84.9 96.0 80.1 84.8 94.7 80.5 5_164 84.7 93.6 80.9 84.8 93.7 81.0 137_164 84.5 95.9 79.7 84.8 95.5 80.3 276_164 84.5 94.9 80.0 84.8 94.9 80.5 164_271 84.1 96.6 78.8 84.8 95.9 80.0 167_164 83.8 97.4 78.0 84.8 97.2 79.4 126_164 84.7 96.8 79.5 84.7 96.1 79.8 211_164 84.3 96.6 79.0 84.7 96.7 79.6 67_164 84.2 95.2 79.4 84.7 93.7 80.9 39_164 83.9 95.9 78.8 84.7 96.1 79.8 186_164 85.1 95.7 80.6 84.6 94.3 80.5 182_164 85.0 96.0 80.3 84.6 94.7 80.4 226_164 85.0 96.0 80.3 84.6 95.1 80.1 27_164 84.7 96.3 79.7 84.6 95.3 80.0 275_164 84.6 95.7 79.8 84.6 94.1 80.5 185_164 84.3 95.8 79.3 84.6 95.1 80.2 92_164 84.2 93.8 80.1 84.6 93.3 80.9 10_164 85.0 95.9 80.4 84.5 94.7 80.1 279_164 84.7 93.3 81.1 84.5 92.7 80.9 256_164 84.7 96.5 79.6 84.5 96.1 79.5 80_164 84.6 94.8 80.2 84.5 93.3 80.8 164_195 84.6 95.6 79.9 84.5 94.9 80.1 243_164 84.5 96.9 79.2 84.5 96.5 79.3 22_164 84.5 95.4 79.8 84.5 94.7 80.1 164_97 84.4 96.4 79.2 84.5 95.9 79.6 34_164 84.2 97.6 78.4 84.5 96.9 79.3 215_164 84.2 95.1 79.5 84.5 94.1 80.4 187_164 84.0 95.1 79.3 84.5 93.7 80.6 164_174 84.0 96.5 78.6 84.5 96.3 79.4 50_164 83.9 95.8 78.8 84.5 94.9 80.0 62_164 83.8 96.9 78.2 84.5 96.7 79.3 75_164 83.8 96.0 78.6 84.5 95.9 79.7 61_164 83.8 95.4 78.9 84.5 95.9 79.6 89_164 83.7 96.6 78.2 84.5 96.1 79.6 306_164 83.6 95.5 78.5 84.5 94.1 80.4 164_286 83.5 97.5 77.6 84.5 96.9 79.3 85_164 84.6 95.6 79.8 84.4 94.9 79.9 192_164 83.9 97.0 78.3 84.4 96.1 79.4 223_164 85.1 95.6 80.6 84.3 94.3 80.1 299_164 84.8 96.4 79.8 84.3 95.1 79.8 73_164 84.5 96.0 79.7 84.3 95.1 79.7 241_164 84.2 96.5 78.9 84.3 95.9 79.4 118_164 84.1 97.0 78.6 84.3 95.9 79.4 283_164 84.1 96.8 78.7 84.3 95.1 79.8 164_77 84.0 96.5 78.6 84.3 95.9 79.3 175_164 83.9 95.2 79.1 84.3 93.5 80.4 164_65 83.8 95.9 78.6 84.3 95.3 79.6 7_164 83.6 96.4 78.2 84.3 95.3 79.6 205_164 83.3 97.3 77.3 84.3 96.5 79.2 188_164 84.2 96.5 78.9 84.2 95.1 79.6 100_164 84.1 94.8 79.5 84.2 94.1 79.9 13_164 84.0 96.2 78.8 84.2 95.7 79.3 106_164 84.0 97.3 78.4 84.2 96.3 79.1 53_164 84.0 95.6 79.0 84.2 93.5 80.3 64_164 83.9 96.1 78.7 84.2 96.1 79.2 210_164 83.9 93.6 79.7 84.2 91.3 81.2 290_164 83.9 95.4 78.9 84.2 94.1 79.9 164_43 83.9 98.1 77.9 84.2 96.3 79.1 164_44 83.9 97.0 78.3 84.2 96.3 79.0 30_164 83.8 95.9 78.7 84.2 95.1 79.6 21_164 83.8 96.4 78.4 84.2 95.9 79.3 301_164 83.8 97.6 77.9 84.2 96.3 79.1 24_164 83.7 97.2 77.9 84.2 96.5 78.9 45_164 83.7 96.9 78.0 84.2 96.7 78.9 200_164 83.7 96.0 78.5 84.2 95.1 79.6 214_164 83.6 96.8 78.0 84.2 95.7 79.3 170_164 83.5 97.0 77.7 84.2 96.3 79.0 213_164 83.5 97.0 77.7 84.2 96.1 79.1 184_164 83.5 97.6 77.5 84.2 97.0 78.8 292_164 83.4 95.4 78.3 84.2 93.7 80.2 171_164 83.3 96.5 77.7 84.2 96.5 79.0 172_164 83.3 97.6 77.3 84.2 97.0 78.8 264_164 84.7 95.4 80.2 84.1 94.3 79.8 70_164 84.2 95.9 79.2 84.1 95.1 79.4 269_164 84.1 95.3 79.3 84.1 94.1 79.8 239_164 84.0 96.9 78.5 84.1 95.9 79.1 71_164 84.0 97.0 78.4 84.1 96.7 78.8 234_164 83.7 97.4 77.9 84.1 96.7 78.8 78_164 83.6 96.1 78.3 84.1 95.3 79.3 96_164 83.6 96.3 78.1 84.1 95.7 79.2 19_164 83.6 97.6 77.7 84.1 96.7 78.8 138_164 83.6 97.0 77.9 84.1 95.7 79.2 245_164 83.3 97.0 77.5 84.1 96.3 78.9 111_164 84.1 94.7 79.6 84.0 94.1 79.7 304_164 84.1 96.2 78.9 84.0 94.9 79.4 250_164 83.9 95.0 79.2 84.0 94.9 79.4 178_164 83.9 96.2 78.6 84.0 94.9 79.4 289_164 83.9 94.9 79.3 84.0 93.7 79.9 84_164 83.9 95.9 78.8 84.0 94.9 79.3 116_164 83.9 95.8 78.8 84.0 94.9 79.3 180_164 83.7 96.7 78.1 84.0 96.1 78.8 94_164 83.7 96.5 78.2 84.0 95.1 79.3 164_253 83.7 96.5 78.3 84.0 95.3 79.3 82_164 83.6 97.0 77.9 84.0 95.9 78.9 132_164 83.6 96.7 78.0 84.0 96.1 78.8 265_164 83.6 94.8 78.8 84.0 93.7 79.8 274_164 83.6 97.4 77.8 84.0 96.1 78.9 164_252 83.6 97.0 78.0 84.0 96.1 78.9 41_164 83.5 96.5 78.0 84.0 95.7 79.1 230_164 83.5 97.0 77.7 84.0 96.5 78.7 191_164 83.5 96.1 78.1 84.0 95.1 79.3 196_164 83.5 96.5 77.9 84.0 96.3 78.8 112_164 83.5 96.9 77.8 84.0 96.3 78.8 280_164 83.4 96.6 77.7 84.0 96.3 78.8 99_164 83.4 97.0 77.6 84.0 96.1 78.8 224_164 83.4 96.3 78.0 84.0 95.7 79.0 193_164 83.4 97.5 77.4 84.0 96.5 78.7 17_164 83.4 97.7 77.3 84.0 96.7 78.6 20_164 83.4 96.5 77.8 84.0 95.5 79.1 164_108 83.4 97.1 77.5 84.0 96.1 78.8 28_164 83.3 96.7 77.6 84.0 95.7 79.1 298_164 83.3 97.3 77.3 84.0 96.5 78.7 240_164 83.3 95.3 78.2 84.0 94.9 79.4 198_164 83.2 97.0 77.3 84.0 96.3 78.8 220_164 84.2 96.7 78.9 83.9 95.7 78.8 124_164 84.1 97.4 78.4 83.9 96.1 78.8 236_164 84.0 94.7 79.5 83.9 93.9 79.7 282_164 83.9 96.0 78.8 83.9 94.9 79.2 235_164 83.9 96.6 78.4 83.9 96.1 78.8 232_164 83.9 95.1 79.2 83.9 93.1 80.0 57_164 83.8 95.5 78.8 83.9 94.3 79.4 277_164 83.8 96.8 78.2 83.9 95.5 78.9 173_164 83.7 96.8 78.1 83.9 95.5 78.9 227_164 83.7 96.0 78.4 83.9 94.9 79.2 69_164 83.7 97.0 78.1 83.9 95.9 78.8 47_164 83.7 97.0 78.0 83.9 95.9 78.8 122_164 83.6 96.5 78.1 83.9 95.5 79.0 242_164 83.6 97.2 77.8 83.9 96.1 78.8 176_164 83.6 97.2 77.7 83.9 96.3 78.6 202_164 83.6 97.3 77.7 83.9 96.1 78.7 197_164 83.6 97.1 77.8 83.9 96.3 78.7 218_164 83.6 97.1 77.9 83.9 96.1 78.8 46_164 83.5 97.0 77.7 83.9 96.3 78.7 86_164 83.5 97.4 77.6 83.9 96.5 78.5 93_164 83.5 97.0 77.8 83.9 96.3 78.6 63_164 83.5 96.5 78.0 83.9 96.1 78.7 109_164 83.5 96.9 77.9 83.9 95.7 78.9 204_164 83.5 96.9 77.8 83.9 95.7 78.8 216_164 83.5 97.1 77.7 83.9 96.3 78.6 169_164 83.5 96.7 77.9 83.9 95.7 78.8 164_254 83.5 96.6 77.9 83.9 95.9 78.8 164_203 83.5 97.0 77.7 83.9 96.3 78.7 98_164 83.4 97.0 77.7 83.9 96.1 78.7 221_164 83.4 97.3 77.5 83.9 96.7 78.4 233_164 83.4 96.0 78.0 83.9 95.1 79.1 284_164 83.4 96.9 77.6 83.9 96.5 78.6 42_164 83.4 97.1 77.6 83.9 96.1 78.8 56_164 83.4 97.2 77.6 83.9 95.9 78.8 296_164 83.4 97.1 77.5 83.9 96.3 78.6 36_164 83.4 97.0 77.6 83.9 96.1 78.8 164_229 83.4 97.1 77.5 83.9 96.7 78.4 134_164 83.3 97.0 77.4 83.9 96.7 78.4 294_164 83.3 97.1 77.3 83.9 96.5 78.5 113_164 83.3 97.3 77.3 83.9 96.5 78.5 164_273 83.3 97.6 77.2 83.9 96.5 78.6 164_238 83.2 97.6 77.1 83.9 97.2 78.3 74_164 83.0 96.9 77.1 83.9 95.9 78.8 102_164 84.5 95.9 79.6 83.8 93.5 79.7 270_164 84.3 95.8 79.4 83.8 93.5 79.6 189_164 84.0 95.5 79.0 83.8 95.1 79.0 262_164 84.0 95.5 79.0 83.8 94.5 79.2 164_58 83.9 94.2 79.5 83.8 92.7 79.9 164_251 83.9 96.0 78.7 83.8 94.1 79.4 103_164 83.8 96.5 78.3 83.8 95.7 78.8 208_164 83.8 97.1 78.1 83.8 96.5 78.4 110_164 83.8 95.5 78.8 83.8 94.5 79.2 281_164 83.7 96.0 78.4 83.8 95.3 78.9 68_164 83.7 96.6 78.1 83.8 95.3 78.8 249_164 83.7 97.0 78.1 83.8 96.5 78.3 219_164 83.6 97.2 77.9 83.8 95.7 78.8 120_164 83.6 96.8 77.9 83.8 95.9 78.7 225_164 83.6 96.5 78.1 83.8 95.3 78.9 52_164 83.6 97.0 77.9 83.8 96.1 78.6 297_164 83.6 97.0 77.9 83.8 95.7 78.7 212_164 83.6 97.0 77.8 83.8 95.9 78.6 248_164 83.6 97.0 77.8 83.8 95.9 78.6 88_164 83.6 97.3 77.8 83.8 96.1 78.6 257_164 83.6 96.8 78.0 83.8 96.1 78.5 244_164 83.6 97.4 77.7 83.8 96.1 78.6 258_164 83.6 97.0 77.9 83.8 95.9 78.7 164_79 83.6 97.3 77.7 83.8 96.3 78.5 181_164 83.5 97.0 77.7 83.8 96.1 78.6 117_164 83.5 97.0 77.7 83.8 96.1 78.5 51_164 83.5 96.7 77.9 83.8 96.1 78.5 209_164 83.5 97.0 77.7 83.8 95.9 78.6 72_164 83.5 96.8 77.9 83.8 96.1 78.6 101_164 83.5 96.8 77.9 83.8 95.7 78.7 59_164 83.5 97.0 77.7 83.8 96.1 78.5 222_164 83.5 96.5 77.9 83.8 95.9 78.6 123_164 83.5 96.8 77.9 83.8 95.7 78.7 266_164 83.5 96.9 77.8 83.8 95.9 78.7 133_164 83.5 97.0 77.7 83.8 95.9 78.6 91_164 83.5 96.7 77.9 83.8 96.1 78.6 35_164 83.5 97.1 77.6 83.8 96.3 78.5 54_164 83.5 97.1 77.7 83.8 96.3 78.5 293_164 83.5 96.9 77.9 83.8 95.9 78.7 291_164 83.5 97.4 77.6 83.8 96.1 78.5 164_267 83.5 97.0 77.8 83.8 96.1 78.6 164_285 83.5 96.4 78.0 83.8 95.9 78.6 164 83.4 97.0 77.7 83.8 95.9 78.6 167_1 81.9 89.1 78.8 82.6 86.0 81.1 166_217 82.3 82.4 82.3 82.3 80.7 83.0 183_169 81.9 89.3 78.7 82.3 89.0 79.4 246_5 81.0 86.8 78.6 82.2 87.6 79.9 3_168 81.3 89.0 78.1 82.0 86.8 80.0 165_2 81.2 90.1 77.4 81.8 90.2 78.3 166_87 82.9 88.5 80.5 81.5 86.6 79.3 60_166 81.3 84.3 80.0 81.5 83.9 80.5 165_136 80.0 94.4 73.9 81.5 94.9 75.7 7_29 80.5 84.8 78.7 81.3 84.1 80.1 49_165 80.4 93.5 74.8 81.3 93.9 75.9 231_165 80.2 92.7 74.8 81.2 92.9 76.2 165_237 80.1 90.4 75.7 81.2 92.3 76.5 2_260 81.0 88.6 77.7 81.0 87.4 78.3 165_288 80.4 93.6 74.8 81.0 94.7 75.1 165_131 80.3 95.7 73.7 81.0 96.1 74.6 303_1 80.2 86.7 77.5 80.8 84.4 79.3 1_15 80.0 86.2 77.4 80.7 83.3 79.6 119_2 80.8 88.6 77.4 80.6 86.8 77.9 135_167 80.6 85.9 78.3 80.6 85.2 78.7 3_228 80.1 83.0 78.8 80.6 81.9 80.1 3_130 80.7 85.0 78.8 80.5 83.3 79.3 2_128 80.6 87.3 77.8 80.5 87.4 77.5 23_2 80.7 87.9 77.6 80.4 86.2 77.9 33_1 80.6 85.8 78.5 80.4 83.5 79.1 194_1 80.5 85.4 78.5 80.4 81.9 79.8 8_1 80.9 87.4 78.1 80.3 82.5 79.4 201_1 80.4 86.1 78.0 80.3 83.3 79.0 125_1 80.0 84.7 78.1 80.3 81.7 79.8 48_1 81.2 88.3 78.2 80.1 82.9 78.9 3_11 80.1 85.2 77.9 80.1 82.1 79.3 105_2 80.1 86.9 77.1 80.1 88.4 76.6 4_179 80.8 81.7 80.4 80.0 82.3 79.1 14_2 80.5 87.8 77.4 80.0 87.4 76.8 2_40 80.4 87.8 77.3 80.0 87.2 77.0 95_2 80.1 87.9 76.8 80.0 86.6 77.2 76_1 80.0 87.0 77.1 80.0 82.7 78.8 114_1 80.0 85.9 77.4 80.0 82.7 78.9

(948) TABLE-US-00007 TABLE 6 SEQ ID NO: Coefficient 1 Coefficient 2 Constant term 18_164 −1.60 2.07 −4.82 255_164 −0.98 2.48 −11.23 177_164 −1.10 2.10 −4.44 4_164 −0.85 1.78 −8.30 164_9 1.73 −0.66 −9.70 300_164 −1.00 2.32 −9.50 272_164 −0.85 1.91 −9.04 206_164 −0.91 2.23 −12.83 12_164 −0.92 2.10 −10.95 166_164 −0.55 1.58 −9.95 168_164 −1.98 1.65 3.77 6_164 −1.20 1.67 −5.70 259_164 −0.82 1.95 −8.42 115_164 −1.79 2.29 −2.81 164_129 1.72 −1.15 −5.57 190_164 −0.48 2.13 −15.45 199_164 −1.10 2.33 −11.65 66_164 −1.88 2.44 −4.75 164_107 2.03 −0.94 −10.10 207_164 −0.64 2.08 −13.57 263_164 −0.56 2.11 −13.68 16_164 −0.88 1.86 −5.46 37_164 −1.04 1.96 −9.42 38_164 −1.07 2.09 −10.66 261_164 −1.03 2.07 −5.02 305_164 −1.09 1.82 −5.02 55_164 −1.62 1.94 −0.70 127_164 −1.50 2.16 −6.33 104_164 0.60 1.44 −17.01 31_164 −0.56 2.05 −14.07 121_164 −1.11 1.74 −5.58 81_164 −0.53 1.74 −11.39 295_164 −1.02 1.89 −7.03 6_165 −1.66 2.22 −5.42 25_164 −0.40 1.88 −13.73 83_164 −0.57 1.59 −9.82 32_164 −2.50 1.64 14.46 247_164 −0.67 1.75 −9.95 26_164 −0.32 1.70 −12.40 302_164 −1.77 1.59 9.32 268_164 −0.92 1.75 −7.57 90_164 −0.98 1.71 −1.22 287_164 −0.85 1.89 −9.10 278_164 1.28 2.03 −32.12 5_164 −1.83 1.84 1.34 137_164 −0.56 1.98 −12.35 276_164 −1.05 1.76 −3.97 164_271 1.61 −0.44 −10.57 167_164 0.63 1.44 −17.66 126_164 −1.58 1.79 −1.86 211_164 −0.88 1.83 −9.18 67_164 −1.06 1.72 −5.62 39_164 −1.38 1.62 −2.09 186_164 0.55 1.66 −17.66 182_164 −0.93 2.15 −9.42 226_164 −0.68 2.13 −10.43 27_164 −0.27 1.80 −13.29 275_164 −1.38 1.65 −1.88 185_164 −0.40 1.75 −11.50 92_164 −0.97 1.81 −6.28 10_164 −0.86 1.79 −9.84 279_164 0.87 1.72 −21.61 256_164 −0.69 1.70 −10.03 80_164 −0.65 2.02 −12.33 164_195 1.96 −0.27 −15.00 243_164 −1.46 1.66 −0.44 22_164 −0.39 1.97 −13.31 164_97 1.69 −0.48 −11.18 34_164 −0.46 1.67 −10.31 215_164 1.34 1.94 −31.62 187_164 −0.51 1.68 −8.56 164_174 1.59 0.59 −17.66 50_164 −0.24 1.85 −14.26 62_164 −0.22 1.65 −12.75 75_164 −0.23 1.77 −13.59 61_164 0.79 1.52 −18.90 89_164 −0.43 1.57 −7.48 306_164 −0.59 1.72 −10.12 164_286 1.45 −0.32 −9.57 85_164 −0.39 1.98 −11.58 192_164 0.78 1.60 −20.45 223_164 −1.58 1.66 0.62 299_164 −0.75 2.07 −10.44 73_164 0.45 1.81 −19.02 241_164 −1.09 1.46 −0.04 118_164 0.71 1.67 −21.70 283_164 0.29 1.54 −14.75 164_77 1.74 −1.41 −2.70 175_164 1.39 1.98 −32.32 164_65 1.68 −0.74 −7.18 7_164 0.43 1.43 −15.72 205_164 −0.92 1.57 −3.72 188_164 −0.14 1.73 −13.43 100_164 −1.13 1.66 −2.07 13_164 −0.12 1.76 −13.99 106_164 −0.71 1.92 −11.57 53_164 −1.10 1.61 0.96 64_164 −0.15 1.69 −13.55 210_164 −1.94 1.61 8.98 290_164 −0.45 1.65 −8.84 164_43 1.88 −0.56 −12.03 164_44 1.66 −0.22 −12.81 30_164 −0.17 1.76 −13.60 21_164 −0.44 1.74 −11.46 301_164 0.22 1.50 −14.48 24_164 −0.37 1.51 −10.00 45_164 −0.46 1.84 −12.20 200_164 −0.47 1.62 −10.00 214_164 −0.45 1.66 −10.68 170_164 −0.15 1.72 −13.87 213_164 −0.41 1.52 −9.71 184_164 −1.04 1.39 −1.69 292_164 −1.29 1.60 −1.13 171_164 −0.13 1.68 −13.66 172_164 0.26 1.46 −13.87 264_164 0.70 1.63 −18.75 70_164 −0.24 1.83 −13.58 269_164 −0.78 1.69 −6.52 239_164 −0.35 1.61 −10.55 71_164 −0.45 1.65 −10.96 234_164 0.38 1.49 −14.91 78_164 −0.19 1.76 −13.93 96_164 −0.14 1.66 −13.34 19_164 0.27 1.52 −14.36 138_164 0.11 1.51 −13.33 245_164 0.34 1.54 −15.75 111_164 0.71 1.38 −17.76 304_164 0.35 1.67 −16.93 250_164 −1.07 1.82 −5.84 178_164 −0.65 1.54 −4.79 289_164 0.36 1.54 −15.62 84_164 0.51 1.64 −17.49 116_164 −1.61 1.54 4.66 180_164 −0.16 1.56 −12.08 94_164 0.22 1.39 −13.09 164_253 1.50 −1.23 2.24 82_164 −0.25 1.57 −11.81 132_164 0.52 1.56 −20.15 265_164 −0.76 1.67 −6.92 274_164 −0.87 1.35 −2.46 164_252 1.51 −0.40 −7.36 41_164 −0.28 1.55 −9.93 230_164 0.39 1.52 −17.97 191_164 −0.96 1.49 −1.36 196_164 −0.13 1.70 −13.61 112_164 −0.12 1.54 −12.28 280_164 0.17 1.50 −13.80 99_164 0.05 1.51 −13.01 224_164 0.33 1.58 −15.79 193_164 −0.38 1.61 −10.63 17_164 0.27 1.48 −14.10 20_164 0.15 1.47 −13.35 164_108 1.51 −0.31 −10.06 28_164 −0.59 1.54 −7.68 298_164 −0.13 1.56 −12.24 240_164 −0.80 1.61 −6.09 198_164 −0.14 1.65 −13.04 220_164 −0.50 1.90 −12.49 124_164 −0.50 1.72 −10.87 236_164 −0.51 1.71 −10.38 282_164 0.37 1.57 −15.84 235_164 0.45 1.60 −17.95 232_164 −0.54 1.69 −8.55 57_164 −0.35 1.91 −13.90 277_164 0.21 1.49 −13.91 173_164 −0.09 1.55 −12.45 227_164 −0.70 1.57 −5.93 69_164 −0.08 1.59 −12.80 47_164 −0.15 1.58 −12.28 122_164 0.10 1.46 −12.92 242_164 −0.07 1.53 −12.07 176_164 −0.29 1.55 −10.76 202_164 −0.36 1.61 −10.87 197_164 −0.08 1.64 −13.36 218_164 −0.51 1.52 −8.70 46_164 0.31 1.49 −14.95 86_164 −0.13 1.55 −12.25 93_164 −0.13 1.52 −11.99 63_164 −0.49 1.60 −9.70 109_164 0.38 1.58 −17.95 204_164 −0.20 1.51 −10.38 216_164 −0.28 1.53 −10.91 169_164 0.20 1.50 −14.62 164_254 1.53 −0.24 −10.19 164_203 1.53 0.17 −14.06 98_164 0.04 1.48 −12.76 221_164 −0.15 1.56 −12.18 233_164 −0.71 1.54 −5.44 284_164 −0.08 1.51 −12.23 42_164 −0.10 1.50 −11.66 56_164 −0.14 1.57 −12.32 296_164 −0.03 1.52 −12.58 36_164 −0.02 1.53 −12.80 164_229 1.51 −0.10 −12.23 134_164 −0.31 1.66 −12.15 294_164 0.11 1.51 −13.40 113_164 −0.24 1.57 −11.89 164_273 1.55 −0.12 −12.21 164_238 1.60 −0.63 −8.26 74_164 0.43 1.47 −17.92 102_164 0.68 1.42 −16.82 270_164 2.03 1.83 −37.88 189_164 0.34 1.52 −15.01 262_164 −0.26 1.62 −11.37 164_58 1.71 0.83 −22.48 164_251 1.63 −0.46 −8.53 103_164 −1.28 1.84 −4.36 208_164 0.68 1.60 −21.40 110_164 −0.50 1.64 −8.76 281_164 −0.36 1.62 −10.57 68_164 −0.12 1.66 −13.02 249_164 −0.44 1.52 −10.19 219_164 −0.30 1.53 −10.58 120_164 0.14 1.46 −13.23 225_164 −0.16 1.67 −12.79 52_164 0.06 1.52 −13.28 297_164 0.05 1.53 −13.21 212_164 0.06 1.52 −13.64 248_164 −0.16 1.54 −11.99 88_164 0.27 1.52 −14.70 257_164 −0.08 1.57 −12.63 244_164 0.25 1.55 −14.58 258_164 −0.30 1.50 −8.85 164_79 1.50 0.13 −13.38 181_164 −0.03 1.53 −12.75 117_164 0.04 1.52 −13.21 51_164 −0.12 1.56 −12.44 209_164 −0.01 1.53 −12.74 72_164 −0.07 1.59 −13.05 101_164 −0.14 1.55 −12.27 59_164 −0.01 1.53 −12.84 222_164 −0.23 1.56 −11.22 123_164 0.07 1.52 −13.33 266_164 0.21 1.54 −15.65 133_164 0.01 1.52 −12.92 91_164 −0.20 1.51 −11.31 35_164 −0.30 1.49 −10.30 54_164 −0.11 1.61 −13.01 293_164 0.06 1.53 −13.43 291_164 −0.15 1.59 −12.36 164_267 1.61 −0.32 −11.40 164_285 1.61 −0.19 −12.48 164 1.52 NA −12.87 167_1 1.12 1.96 −28.15 166_217 −0.69 1.95 −10.62 183_169 −4.31 3.31 14.07 246_5 3.66 −3.20 −2.97 3_168 1.58 −1.82 6.03 165_2 1.07 0.64 −12.10 166_87 −0.74 0.95 −0.57 60_166 0.88 −0.48 −1.19 165_136 1.72 −0.72 −8.51 7_29 1.53 0.90 −18.05 49_165 −1.32 1.80 −1.73 231_165 0.32 1.27 −12.22 165_237 1.91 −0.81 −7.22 2_260 0.72 0.50 −6.78 165_288 2.06 −1.38 −3.16 165_131 1.75 −0.84 −7.21 303_1 0.47 1.93 −20.83 1_15 1.91 0.36 −20.23 119_2 −0.51 1.19 −4.27 135_167 0.83 0.98 −12.50 3_228 1.32 0.32 −10.30 3_130 1.22 0.90 −14.91 2_128 0.95 0.77 −10.55 23_2 0.39 0.88 −7.42 33_1 0.44 1.82 −19.51 194_1 0.96 2.15 −30.54 8_1 0.69 2.03 −23.35 201_1 0.56 1.75 −20.94 125_1 0.73 2.11 −28.03 48_1 0.61 2.08 −23.93 3_11 1.45 −0.64 −4.99 105_2 0.51 0.97 −8.76 4_179 −0.78 2.02 −8.19 14_2 −0.38 1.01 −3.29 2_40 0.74 0.42 −6.86 95_2 0.94 0.94 −12.41 76_1 0.40 1.90 −20.30 114_1 0.42 1.97 −20.95

Example 2

(949) <Discriminant Analysis Using Up to Five miRNAs in Combination>

(950) In this Example, discriminants were prepared using one to five gene markers in the training cohort including the lung cancer patients and the test subjects without lung cancer (Table 11b1), and then, the discriminant performance was evaluated in the validation cohort (Table 11b2). Based on the evaluation, genes used in discriminants with high performance were extracted to obtain gene markers that were able to detect lung cancer.

(951) To be more specific, firstly, the miRNA expression levels of the training cohort and the validation cohort obtained in the preceding Reference Examples were combined and normalized by global normalization. Secondly, in order to acquire diagnostic markers with higher reliability, only 396 genes having the gene expression level of 2.sup.6 or higher in 50% or more of the samples in either of the positive sample group (lung cancer patients) or the negative sample group (healthy subjects, benign bone and soft tissue tumor patients and benign breast disease patients and patients having a cancer other than lung cancer), were selected as analytes.

(952) Thirdly, combinations of one to five genes of the 396 gene above were subjected to the Fisher's discriminant analysis using the 396 gene expression level measurement values described above to construct discriminants for discriminating the presence or absence of lung cancer. In this relation, discriminants with high discriminant performance were searched for using a modified greedy algorithm. Accuracy, sensitivity, and specificity in the validation cohort were further calculated using the discriminants prepared above, and the discriminant performance was validated using independent samples. As a result, total 750 discriminants including top 150 discriminants having higher performance as to the combinations of one to five genes were obtained. The genes contained in these discriminants were selected as other diagnostic markers for the lung cancer patients and the test subjects without lung cancer. In this way, miR-920, miR-1185-1-3p, miR-4327, miR-5739, miR-1185-2-3p, miR-1238-5p, miR-1246, miR-1470, miR-197-5p, miR-208a-5p, miR-2467-3p, miR-3122, miR-3160-5p, miR-320b, miR-3610, miR-3619-3p, miR-3937, miR-4447, miR-4480, miR-4505, miR-4515, miR-4535, miR-4706, miR-4718, miR-4730, miR-4734, miR-4755-3p, miR-4787-3p, miR-5008-5p, miR-5010-5p, miR-504-3p, miR-5100, miR-557, miR-6510-5p, miR-6511b-5p, miR-6515-3p, miR-6722-5p, miR-6737-5p, miR-6766-5p, miR-6769a-5p, miR-6771-5p, miR-6786-5p, miR-6794-5p, miR-6800-3p, miR-6802-5p, miR-6805-3p, miR-6819-5p, miR-6824-5p, miR-6858-5p, miR-6861-5p, miR-6880-3p, miR-7107-5p, miR-7109-5p, miR-7114-5p, miR-8071, miR-204-3p, miR-3154, miR-3960, miR-4433a-5p, miR-4462, miR-4476, miR-4508, miR-4687-3p, miR-4732-5p, miR-4771, miR-642a-3p, miR-6732-5p, miR-6820-5p, miR-6821-5p, miR-6829-5p, miR-6893-5p, miR-7108-3p, miR-7111-5p, miR-885-3p, miR-1343-3p, miR-6746-5p, miR-422a, miR-4632-5p, miR-6791-5p, miR-1225-3p, miR-1233-5p, miR-1268a, miR-1268b, miR-1273g-3p, miR-1290, miR-150-3p, miR-17-3p, miR-1908-5p, miR-1914-3p, miR-296-3p, miR-3131, miR-3162-5p, miR-3197, miR-320a, miR-342-5p, miR-365a-5p, miR-3679-5p, miR-371a-5p, miR-423-5p, miR-4257, miR-4270, miR-4286, miR-4417, miR-4442, miR-4454, miR-4507, miR-4516, miR-451a, miR-4665-3p, miR-4675, miR-4689, miR-4695-5p, miR-4739, miR-4745-5p, miR-5001-5p, miR-5698, miR-6075, miR-6125, miR-614, miR-615-5p, miR-638, miR-650, miR-6717-5p, miR-6721-5p, miR-6741-5p, miR-6752-5p, miR-6780b-5p, miR-6784-5p, miR-6875-5p, miR-744-5p, miR-760, miR-7977, miR-8059, miR-8063, miR-8072, miR-92a-2-5p, miR-1228-3p, miR-1275, miR-1307-3p, miR-29b-3p, miR-3135b, miR-3185, miR-4532, miR-4690-5p, miR-4758-5p, miR-4783-3p, miR-6131, miR-625-3p, miR-6511a-5p, miR-6765-3p, miR-6816-5p, miR-6825-5p, miR-6845-5p, miR-7150, and miR-7975, and the relevant polynucleotides consisting of nucleotide sequences of SEQ ID NOs: 2, 4, 5, 6, 9, 12, 13, 17, 18, 19, 22, 23, 27, 31, 33, 34, 39, 47, 50, 55, 57, 59, 66, 70, 73, 74, 78, 80, 81, 82, 83, 85, 88, 93, 94, 95, 99, 102, 106, 107, 108, 109, 111, 114, 115, 117, 121,123, 126 to 131, 136, 139 to 142, 144, 145, 146, 147, 149 to 152, 155 to 160, 162, 164, 165, 166, 168, 169, 173, 177, 183, 184, 185, 188 to 191, 193, 199, 201, 202, 205, 206, 207, 211, 213, 214, 216, 217, 218, 220, 222, 223, 226, 229, 230, 231, 234, 236, 237, 238, 241, 242, 246, 249, 250, 253, 255, 256, 258, 260, 263, 264, 268, 270, 276, 278, 286, 295, 296, 299 to 302, 304, 307, 308, 309, 312 to 326, and 328, were found. Among them, the genes newly found as the marker for examining the presence or absence of lung cancer are polynucleotides consisting of the nucleotide sequences represented by SEQ ID NOs: 164, 165, 166, 168, 169, 173, 177, 183, 184, 185, 188 to 191, 193, 199, 201, 202, 205, 206, 207, 211, 213, 214, 216, 217, 218, 220, 222, 223, 226, 229, 230, 231, 234, 236, 237, 238, 241, 242, 246, 249, 250, 253, 255, 256, 258, 260, 263, 264, 268, 270, 276, 278, 286, 295, 296, 299 to 302, 304, 307, 308, 309, 312 to 326, and 328.

(953) The sensitivities in the validation cohort determined by the discriminants obtained using any single one of the 88 polynucleotides consisting of the nucleotide sequences represented by SEQ ID NOs: 188, 164, 85, 13, 231, 319, 263, 165, 226, 94, 190, 328, 80, 220, 316, 2, 115, 299, 50, 150, 31, 318, 149, 312, 70, 127, 183, 66, 12, 255, 162, 199, 222, 278, 260, 246, 22, 106, 322, 57, 309, 184, 206, 207, 201, 217, 317, 300, 102, 159, 73, 78, 315, 107, 23, 33, 307, 114, 185, 128, 109, 59, 236, 214, 140, 99, 144, 47, 241, 321, 130, 95, 142, 234, 286, 173, 320, 314, 111, 27, 304, 177, 74, 34, 17, 211, 193, and 256 among the polynucleotides described above are shown in Table 3. Also, discriminant coefficients and constant terms are shown in Table 4. In this context, the general sensitivity of the existing marker CEA has been reported as being 69%. Accordingly, it was demonstrated that the polynucleotides represented by these SEQ ID NOs singly detect lung cancer with sensitivity beyond CEA.

(954) The genes represented by SEQ ID NOs: 2, 4, 5, 6, 9, 12, 13, 17, 18, 19, 22, 23, 27, 31, 33, 34, 39, 47, 50, 55, 57, 59, 66, 70, 73, 74, 78, 80, 81, 82, 83, 85, 88, 93, 94, 95, 99, 102, 106, 107, 108, 109, 111, 114, 115, 117, 121, 123, 126 to 131, 136, 139 to 142, 144, 145, 146, 147, 149 to 152, 155 to 160, 162, 164, 165, 166, 168, 169, 173, 177, 183, 184, 185, 188 to 191, 193, 199, 201, 202, 205, 206, 207, 211, 213, 214, 216, 217, 218, 220, 222, 223, 226, 229, 230, 231, 234, 236, 237, 238, 241, 242, 246, 249, 250, 253, 255, 256, 258, 260, 263, 264, 268, 270, 276, 278, 286, 295, 296, 299 to 302, 304, 307, 308, 309, 312 to 326, and 328 provide excellent lung cancer discriminant performance, when the genes are used not only alone but also in combinations of, for example, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more genes. For example, when a discriminant was prepared using gene expression level of the nucleotide sequence represented by SEQ ID NO: 18 alone, the discrimination accuracy in the validation cohort was 61.6%; however, when a discriminant was prepared using two genes (SEQ ID NOs: 18 and 164) in combination, the discrimination accuracy in the validation cohort was 86.7%, if a discriminant was prepared using three genes (SEQ ID NOs: 18, 164 and 255), the discrimination accuracy in the validation cohort was 88.2%, when a discriminant was prepared using four genes (SEQ ID NOs: 18, 121, 130 and 164), the discrimination accuracy in the validation cohort was 88.6%, and when a discriminant was prepared using five genes (SEQ ID NOs: 18, 121, 130, 136 and 164), the discrimination accuracy in the validation cohort was 88.8%.

(955) As to the discriminant prepared using measurement values of nucleotide sequences represented by SEQ ID NOs: 164, 18, 268, 147 and 184 in combination, discriminant scores of 1,186 lung cancer patients and 2,777 test subjects without lung cancer in the training cohort were significantly separated, as shown in the upper panel of FIG. 2.

(956) The same results were able to be reproduced also in the validation cohort (FIG. 2, lower panel).

(957) The discriminant scores were categorized on the basis of the histological types and stages of the lung cancer patients. As a result, it was confirmed that lung cancer in all of the categories was able to be detected with high sensitivity (FIG. 3).

(958) Of the 750 discriminants obtained above, the number of discriminants exhibiting a discrimination accuracy of 85% or more both in the training cohort and the validation cohort was 305. These discriminants having particularly high discriminant performance contained at least one of the genes represented by SEQ ID NOs: 18, 4, 130, 2, 9, 17, and 121. These seven genes are referred to as “cancer type-specific polynucleotide group”.

(959) Specifically, when measurement was carried out using a polynucleotide consisting of the nucleotide sequence represented by SEQ ID NO: 18 or a complementary sequence thereof as a target nucleic acid, discrimination accuracy is shown in Table 7-1. The measurement using a combination of 2, 3, 4 or 5 genes comprising the polynucleotide consisting of the nucleotide sequence represented by SEQ ID NO: 18 or a complementary sequence thereof exhibited the highest accuracy of 86.7%, 88.2%, 88.6% and 88.8%, respectively, in the validation cohort.

(960) Further, when measurement was carried out using a polynucleotide consisting of the nucleotide sequence represented by SEQ ID NO: 4 or a complementary sequence thereof as a target nucleic acid, discrimination accuracy is shown in Table 7-2. The measurement using a combination of 2, 3, 4 or 5 genes comprising the polynucleotide consisting of the nucleotide sequence represented by SEQ ID NO: 4 or a complementary sequence thereof exhibited the highest accuracy of 86.0%, 87.1%, 87.8% and 87.8%, respectively, in the validation cohort.

(961) Further, when measurement was carried out using a polynucleotide consisting of the nucleotide sequence represented by SEQ ID NO: 130 or a complementary sequence thereof as a target nucleic acid, discrimination accuracy is shown in Table 7-3. The measurement using a combination of 3, 4 or 5 genes comprising the polynucleotide consisting of the nucleotide sequence represented by SEQ ID NO: 130 or a complementary sequence thereof exhibited the highest accuracy of 86.9%, 88.6% and 88.8%, respectively, in the validation cohort.

(962) Further, when measurement was carried out using a polynucleotide consisting of the nucleotide sequence represented by SEQ ID NO: 2 or a complementary sequence thereof as a target nucleic acid, discrimination accuracy is shown in Table 7-4. The measurement using a combination of 4 or 5 genes comprising the polynucleotide consisting of the nucleotide sequence represented by SEQ ID NO: 2 or a complementary sequence thereof exhibited the highest accuracy of 86.3% and 87.8%, respectively, in the validation cohort.

(963) Further, when measurement was carried out using a polynucleotide consisting of the nucleotide sequence represented by SEQ ID NO: 9 or a complementary sequence thereof as a target nucleic acid, discrimination accuracy is shown in Table 7-5. The measurement using a combination of 3, 4 or 5 genes comprising the polynucleotide consisting of the nucleotide sequence represented by SEQ ID NO: 9 or a complementary sequence thereof exhibited the highest accuracy of 86.9%, 87.2% and 87.6%, respectively, in the validation cohort.

(964) Further, when measurement was carried out using a polynucleotide consisting of the nucleotide sequence represented by SEQ ID NO: 17 or a complementary sequence thereof as a target nucleic acid, discrimination accuracy is shown in Table 7-6. The measurement using a combination of 3, 4 or 5 genes comprising the polynucleotide consisting of the nucleotide sequence represented by SEQ ID NO: 17 or a complementary sequence thereof exhibited the highest accuracy of 85.6%, 87.5% and 87.8%, respectively, in the validation cohort.

(965) Further, when measurement was carried out using a polynucleotide consisting of the nucleotide sequence represented by SEQ ID NO: 121 or a complementary sequence thereof as a target nucleic acid, discrimination accuracy is shown in Table 7-7. The measurement using a combination of 3, 4 or 5 genes comprising the polynucleotide consisting of the nucleotide sequence represented by SEQ ID NO: 121 or a complementary sequence thereof exhibited the highest accuracy of 86.9%, 88.6% and 88.8%, respectively, in the validation cohort.

(966) Further, lung adenocarcinoma, lung squamous cell carcinoma, small cell lung carcinoma and large cell lung carcinoma were able to be detected with average sensitivities of 96.4%, 97.1%, 97.8% and 97.6%, respectively, determined by the 305 discriminants obtained using the polynucleotides consisting of SEQ ID NOs described in Tables 7-1 to 7-7 in combination. In addition, stage I (IA and IIA), stage II (IIA and IIB), and stage III/IV (IIIA, IIIB and IV) of lung cancer were able to be detected with average sensitivities of 96.9%, 94.0% and 94.6%, respectively, determined by the 305 discriminants obtained using the polynucleotides consisting of SEQ ID NOs described in Tables 7-1 to 7-7 in combination. Accordingly, the polynucleotides obtained in this Example exerted a high detection ability without missing a particular histological type or stage of progression of lung cancer.

(967) From the above-mentioned results, the polynucleotides consisting of the nucleotide sequences of SEQ ID NOs: 2, 4, 5, 6, 9, 12, 13, 17, 18, 19, 22, 23, 27, 31, 33, 34, 39, 47, 50, 55, 57, 59, 66, 70, 73, 74, 78, 80, 81, 82, 83, 85, 88, 93, 94, 95, 99, 102, 106, 107, 108, 109, 111, 114, 115, 117, 121, 123, 126 to 131, 136, 139 to 142, 144, 145, 146, 147, 149 to 152, 155 to 160, 162, 164, 165, 166, 168, 169, 173, 177, 183, 184, 185, 188 to 191, 193, 199, 201, 202, 205, 206, 207, 211, 213, 214, 216, 217, 218, 220, 222, 223, 226, 229, 230, 231, 234, 236, 237, 238, 241, 242, 246, 249, 250, 253, 255, 256, 258, 260, 263, 264, 268, 270, 276, 278, 286, 295, 296, 299 to 302, 304, 307, 308, 309, 312 to 326, and 328, obtained in this Example, are deemed to be gene groups that lung cancer patients can be specifically discriminated from any of healthy subjects, benign bone and soft tissue tumor patients and benign breast disease patients, and patients having a cancer other than lung cancer. It was further demonstrated that high lung cancer discriminant performance can be obtained by using multiple polynucleotides in combination as target nucleic acids rather than using a single polynucleotide or fewer polynucleotides in combination. In this relation, particularly high discriminant performance can be obtained by using the polynucleotides contained in the cancer type-specific polynucleotide group in combination, wherein the combination of the multiple polynucleotides is not limited to those mentioned above. Even if the polynucleotides are used in any combination, lung cancer can be detected.

(968) Specifically, as shown in the preceding Examples 1 or 2, it is concluded that in all of the polynucleotides consisting of the nucleotide sequences represented by SEQ ID NOs: 1 to 329 or complementary sequences thereof as the target nucleic acids, there exist combinations of 1, 2, 3, 4 or 5 genes that exhibit discriminant performance beyond the existing lung cancer markers, thus indicating that the polynucleotides are excellent diagnostic markers for lung cancer that can detect any histological type or stage of progression of lung cancer described in the preceding Reference Example.

(969) TABLE-US-00008 TABLE 7-1 Combined Validation cohort gene number SEQ ID NO: Sensitivity Specificity Accuracy 2 18_164 98.2 81.8 86.7 3 18_164_255 98.2 83.9 88.2 3 18_164_300 97.8 83.0 87.5 3 18_164_190 97.6 83.0 87.4 3 18_85_164 97.2 83.2 87.4 3 18_147_164 98.2 82.5 87.2 3 18_22_164 97.4 82.8 87.2 3 18_164_312 98.2 82.3 87.1 3 18_66_164 97.8 82.5 87.1 3 18_78_164 97.8 82.4 87.0 3 18_27_164 97.4 82.5 87.0 3 18_164_207 98.2 82.0 86.9 3 18_82_164 98.0 82.1 86.9 3 18_164_263 98.4 81.9 86.8 3 18_164_168 98.2 82.0 86.8 3 18_34_164 98.0 82.0 86.8 3 18_39_164 97.6 82.1 86.8 3 18_57_164 97.6 82.2 86.8 3 18_121_164 98.6 81.6 86.7 3 18_107_164 98.2 81.8 86.7 3 18_70_164 97.6 82.0 86.7 3 18_50_164 97.6 82.0 86.7 3 18_164_250 96.9 82.4 86.7 3 18_164_315 98.2 81.6 86.6 3 18_164_211 98.0 81.8 86.6 3 18_164_326 97.2 82.1 86.6 3 18_164_308 98.4 81.3 86.4 3 18_164_268 98.2 81.4 86.4 3 18_164_191 97.8 81.4 86.3 3 18_149_165 95.5 81.2 85.5 4 18_121_130_164 98.6 84.4 88.6 4 18_164_255_316 98.4 84.3 88.5 4 18_121_164_255 98.0 84.2 88.4 4 18_147_164_255 98.0 84.3 88.4 4 18_27_164_255 97.8 84.3 88.4 4 18_34_164_255 98.0 84.1 88.3 4 18_47_164_255 98.2 84.0 88.2 4 18_158_164_255 98.0 84.1 88.2 4 18_164_220_255 98.0 84.0 88.2 4 18_88_164_255 97.8 84.1 88.2 4 18_130_164_268 98.4 83.7 88.1 4 18_164_255_321 98.2 83.8 88.1 4 18_164_184_255 98.2 83.7 88.1 4 18_152_164_255 98.0 83.8 88.1 4 18_164_185_255 98.0 83.9 88.1 4 18_164_238_255 98.0 83.8 88.1 4 18_164_255_256 97.8 83.9 88.1 4 18_127_164_255 97.6 84.1 88.1 4 18_164_222_255 98.2 83.6 88.0 4 18_139_164_255 98.0 83.7 88.0 4 18_39_164_255 97.6 83.9 88.0 4 18_164_255_295 96.9 84.2 88.0 4 18_146_164_255 97.6 83.7 87.9 4 18_164_211_255 97.4 83.7 87.8 4 18_164_255_322 97.4 83.7 87.8 4 18_164_255_318 98.0 83.3 87.7 4 18_121_164_201 98.2 83.0 87.6 4 18_147_164_300 98.2 83.1 87.6 4 18_121_151_164 98.2 83.1 87.6 4 18_164_211_300 97.2 83.0 87.3 4 18_95_164_268 98.8 82.0 87.1 4 18_164_231_268 98.4 82.2 87.1 4 18_147_164_268 98.4 82.2 87.1 4 18_164_188_268 98.2 82.4 87.1 4 18_164_268_312 98.0 82.5 87.1 4 18_39_164_300 97.4 82.6 87.1 4 18_95_121_164 99.0 81.5 86.8 4 18_93_164_268 98.6 81.7 86.8 4 18_164_268_308 98.6 81.6 86.7 4 18_107_121_164 98.6 81.6 86.7 4 18_164_218_268 98.4 81.5 86.6 4 18_164_202_268 98.2 81.6 86.6 4 13_18_130_165 98.2 81.5 86.5 4 18_149_165_168 96.7 82.1 86.5 4 18_164_242_268 98.2 81.5 86.5 4 18_164_214_268 98.2 81.5 86.5 4 18_164_268_313 98.2 81.4 86.5 4 18_162_164_268 98.0 81.5 86.5 4 18_150_164_268 98.0 81.6 86.5 4 18_164_268_315 98.6 81.2 86.4 4 18_152_164_268 98.6 81.2 86.4 4 18_164_268_325 98.2 81.4 86.4 4 18_121_149_165 97.1 81.7 86.3 4 13_18_165_260 98.6 80.8 86.1 4 13_18_165_268 98.8 80.6 86.1 4 13_18_121_165 99.2 80.4 86.1 4 13_18_165_168 98.2 80.9 86.1 4 18_149_165_268 96.1 81.7 86.0 4 13_18_83_165 98.0 80.9 86.0 4 13_18_165_263 98.6 80.5 85.9 4 2_18_165_268 95.5 81.7 85.8 4 13_18_165_211 98.2 80.4 85.8 4 13_18_165_256 98.2 80.4 85.7 4 13_18_165_276 98.0 80.2 85.5 4 13_18_165_302 98.0 80.1 85.5 4 13_18_165_190 98.2 79.9 85.3 5 18_121_130_136_164 98.6 84.6 88.8 5 18_121_130_164_314 98.4 84.6 88.8 5 18_114_121_130_164 99.0 84.3 88.7 5 18_121_130_164_214 98.6 84.5 88.7 5 18_121_130_164_193 98.8 84.3 88.6 5 18_130_164_255_268 98.6 84.4 88.6 5 18_121_130_164_320 98.6 84.4 88.6 5 18_121_130_164_301 98.6 84.3 88.6 5 18_121_130_144_164 98.6 84.4 88.6 5 18_121_130_164_168 98.4 84.5 88.6 5 18_121_130_164_205 98.4 84.4 88.6 5 18_121_130_158_164 98.8 84.1 88.5 5 18_121_130_164_260 98.8 84.1 88.5 5 18_106_121_130_164 98.8 84.1 88.5 5 18_121_130_164_318 98.6 84.2 88.5 5 18_121_130_164_286 98.6 84.1 88.5 5 18_121_130_164_315 98.6 84.2 88.5 5 18_121_130_164_237 98.6 84.2 88.5 5 18_121_130_164_184 98.6 84.2 88.5 5 18_121_130_164_270 98.4 84.2 88.5 5 18_121_130_164_309 98.4 84.2 88.5 5 18_121_130_164_278 98.4 84.3 88.5 5 18_82_121_130_164 98.4 84.2 88.5 5 18_23_121_130_164 98.4 84.2 88.5 5 18_121_130_164_189 98.4 84.3 88.5 5 18_121_130_152_164 98.2 84.3 88.5 5 18_121_130_164_213 98.2 84.3 88.5 5 18_121_130_164_229 98.2 84.3 88.5 5 18_57_121_130_164 98.2 84.4 88.5 5 18_121_130_142_164 98.8 83.9 88.4 5 18_121_130_155_164 98.6 84.0 88.4 5 18_39_121_130_164 98.4 84.1 88.4 5 18_27_130_164_268 98.4 84.1 88.4 5 18_33_121_130_164 98.4 84.1 88.4 5 18_121_126_130_164 98.4 84.1 88.4 5 18_121_130_164_319 98.4 84.1 88.4 5 18_22_121_130_164 98.2 84.1 88.4 5 18_59_121_130_164 98.2 84.1 88.4 5 18_27_121_130_164 97.8 84.4 88.4 5 18_130_164_268_317 98.2 84.1 88.3 5 18_121_130_164_201 98.2 84.1 88.3 5 18_34_164_211_255 97.6 84.3 88.3 5 18_19_121_130_164 98.4 83.9 88.2 5 18_74_130_164_268 98.4 83.7 88.1 5 18_130_164_264_268 97.2 84.1 88.0 5 18_39_164_255_328 97.4 83.9 87.9 5 18_39_164_226_255 97.4 83.9 87.9 5 18_95_121_164_188 99.0 83.0 87.8 5 13_18_121_130_165 98.4 82.5 87.2 5 13_18_130_165_268 98.6 82.3 87.2 5 18_151_164_268_315 98.0 82.3 87.0 5 18_147_164_184_268 98.8 81.9 86.9 5 18_149_165_168_268 96.7 82.6 86.8 5 13_18_165_268_276 98.0 81.3 86.3 5 2_18_165_268_301 95.3 82.2 86.1 5 2_18_165_268_315 96.3 81.8 86.1 5 13_18_165_183_268 99.0 80.2 85.8 5 13_18_165_184_268 99.0 80.1 85.8

(970) TABLE-US-00009 TABLE 7-2 Combined Validation cohort gene number SEQ ID NO: Sensitivity Specificity Accuracy 2 4_164 91.3 83.7 86.0 3 4_165_168 95.3 83.5 87.1 4 4_165_168_246 97.4 83.7 87.8 4 4_128_165_168 96.3 84.0 87.6 4 4_117_165_168 96.5 83.8 87.6 4 4_159_165_168 95.5 84.1 87.5 4 4_165_168_260 95.3 84.2 87.5 4 4_17_165_168 95.1 84.2 87.5 4 4_165_168_173 96.3 83.6 87.4 4 4_80_165_168 96.5 82.6 86.8 4 4_99_165_168 94.5 83.4 86.7 4 2_4_168_246 93.3 82.8 85.9 4 4_17_115_168 92.1 83.3 85.9 4 4_17_115_302 89.8 84.1 85.8 4 4_94_173_183 93.9 82.2 85.7 4 2_4_173_183 93.3 82.2 85.5 4 2_4_115_168 90.8 83.3 85.5 4 4_17_115_184 91.5 82.7 85.3 5 4_17_165_168_173 96.5 84.1 87.8 5 4_17_165_168_223 95.7 84.5 87.8 5 4_128_129_165_168 94.5 84.9 87.8 5 2_4_130_168_246 95.9 84.3 87.8 5 4_17_128_165_168 95.5 84.4 87.7 5 4_17_165_168_169 95.3 84.5 87.7 5 4_17_117_165_168 95.3 84.4 87.6 5 4_17_165_168_323 95.3 84.3 87.6 5 4_17_81_165_168 94.7 84.6 87.6 5 4_17_165_168_253 95.1 84.4 87.6 5 4_17_162_165_168 95.5 84.2 87.6 5 2_4_168_201_246 94.5 84.7 87.6 5 4_17_141_165_168 94.7 84.5 87.5 5 4_17_129_165_168 94.3 84.6 87.5 5 4_17_165_168_258 94.7 84.4 87.5 5 4_17_165_168_190 95.7 84.0 87.5 5 4_17_115_168_177 92.7 85.3 87.5 5 4_17_165_168_191 94.9 84.2 87.4 5 4_17_158_165_168 95.3 84.1 87.4 5 4_17_165_168_184 95.7 83.9 87.4 5 4_17_94_165_168 95.3 84.1 87.4 5 4_17_165_168_296 95.5 83.9 87.4 5 4_17_165_168_307 95.1 84.1 87.4 5 4_17_123_165_168 95.5 83.9 87.4 5 4_17_39_165_168 94.9 84.1 87.4 5 4_17_145_165_168 95.3 83.9 87.3 5 4_17_165_168_286 94.9 84.1 87.3 5 4_17_73_165_168 95.3 83.8 87.2 5 4_17_115_165_168 94.9 84.0 87.2 5 4_17_108_165_168 94.7 84.1 87.2 5 4_17_156_165_168 94.9 84.0 87.2 5 4_17_165_168_249 95.5 83.6 87.2 5 4_17_131_165_168 95.3 83.7 87.2 5 4_17_165_168_304 94.9 83.9 87.2 5 4_17_157_165_168 95.1 83.8 87.2 5 4_17_165_168_318 94.9 83.8 87.1 5 4_17_74_165_168 94.3 84.1 87.1 5 4_17_165_168_216 94.9 83.6 87.0 5 4_17_165_168_309 94.5 83.8 87.0 5 4_17_165_168_236 94.7 83.7 87.0 5 4_17_165_168_324 95.3 83.5 87.0 5 2_4_111_168_173 92.7 84.5 86.9 5 4_17_115_130_168 92.7 84.3 86.8 5 2_4_130_168_173 93.7 83.9 86.8 5 4_17_111_115_168 91.9 84.6 86.8 5 2_4_168_173_201 93.5 83.7 86.6 5 4_17_115_160_168 92.1 84.3 86.6 5 4_17_115_168_246 94.1 83.5 86.6 5 2_4_115_168_173 94.3 83.3 86.6 5 4_17_115_168_201 92.3 84.1 86.5 5 4_17_115_168_217 92.9 83.8 86.5 5 2_4_17_115_168 92.5 83.6 86.3 5 4_17_115_140_168 90.9 84.1 86.1 5 4_17_102_115_168 92.1 83.3 85.9

(971) TABLE-US-00010 TABLE 7-3 Combined Validation cohort gene number SEQ ID NO: Sensitivity Specificity Accuracy 3 121_130_164 97.6 82.3 86.9 4 18_121_130_164 98.6 84.4 88.6 4 18_130_164_268 98.4 83.7 88.1 4 13_18_130_165 98.2 81.5 86.5 5 18_121_130_136_164 98.6 84.6 88.8 5 18_121_130_164_314 98.4 84.6 88.8 5 18_114_121_130_164 99.0 84.3 88.7 5 18_121_130_164_214 98.6 84.5 88.7 5 18_121_130_164_193 98.8 84.3 88.6 5 18_130_164_255_268 98.6 84.4 88.6 5 18_121_130_164_320 98.6 84.4 88.6 5 18_121_130_164_301 98.6 84.3 88.6 5 18_121_130_144_164 98.6 84.4 88.6 5 18_121_130_164_168 98.4 84.5 88.6 5 18_121_130_164_205 98.4 84.4 88.6 5 18_121_130_158_164 98.8 84.1 88.5 5 18_121_130_164_260 98.8 84.1 88.5 5 18_106_121_130_164 98.8 84.1 88.5 5 18_121_130_164_318 98.6 84.2 88.5 5 18_121_130_164_286 98.6 84.1 88.5 5 18_121_130_164_315 98.6 84.2 88.5 5 18_121_130_164_237 98.6 84.2 88.5 5 18_121_130_164_184 98.6 84.2 88.5 5 18_121_130_164_270 98.4 84.2 88.5 5 18_121_130_164_309 98.4 84.2 88.5 5 18_121_130_164_278 98.4 84.3 88.5 5 18_82_121_130_164 98.4 84.2 88.5 5 18_23_121_130_164 98.4 84.2 88.5 5 18_121_130_164_189 98.4 84.3 88.5 5 18_121_130_152_164 98.2 84.3 88.5 5 18_121_130_164_213 98.2 84.3 88.5 5 18_121_130_164_229 98.2 84.3 88.5 5 18_57_121_130_164 98.2 84.4 88.5 5 18_121_130_142_164 98.8 83.9 88.4 5 18_121_130_155_164 98.6 84.0 88.4 5 18_39_121_130_164 98.4 84.1 88.4 5 18_27_130_164_268 98.4 84.1 88.4 5 18_33_121_130_164 98.4 84.1 88.4 5 18_121_126_130_164 98.4 84.1 88.4 5 18_121_130_164_319 98.4 84.1 88.4 5 18_22_121_130_164 98.2 84.1 88.4 5 18_59_121_130_164 98.2 84.1 88.4 5 18_27_121_130_164 97.8 84.4 88.4 5 18_130_164_268_317 98.2 84.1 88.3 5 18_121_130_164_201 98.2 84.1 88.3 5 18_19_121_130_164 98.4 83.9 88.2 5 18_74_130_164_268 98.4 83.7 88.1 5 18_130_164_264_268 97.2 84.1 88.0 5 2_4_130_168_246 95.9 84.3 87.8 5 2_9_130_168_246 95.9 84.0 87.5 5 13_18_121_130_165 98.4 82.5 87.2 5 13_18_130_165_268 98.6 82.3 87.2 5 4_17_115_130_168 92.7 84.3 86.8 5 2_4_130_168_173 93.7 83.9 86.8 5 2_9_130_168_173 93.7 83.2 86.3 5 2_111_130_168_173 93.3 83.0 86.1 5 2_83_130_168_173 94.5 82.2 85.9 5 2_6_130_168_173 94.5 82.0 85.7 5 2_6_130_173_184 95.9 81.3 85.6 5 2_130_168_173_213 94.9 81.4 85.4 5 2_5_130_168_173 92.9 82.1 85.3 5 2_130_168_173_249 93.9 81.5 85.2

(972) TABLE-US-00011 TABLE 7-4 Combined Validation cohort gene number SEQ ID NO: Sensitivity Specificity Accuracy 4 2_121_165_168 95.3 82.5 86.3 4 2_165_168_268 94.9 82.0 85.9 4 2_4_168_246 93.3 82.8 85.9 4 2_18_165_268 95.5 81.7 85.8 4 2_4_173_183 93.3 82.2 85.5 4 2_4_115_168 90.8 83.3 85.5 4 2_9_168_246 93.3 82.1 85.5 4 2_111_168_246 92.7 82.3 85.4 4 2_111_168_173 92.9 82.1 85.3 4 2_102_168_246 93.1 81.7 85.1 5 2_4_130_168_246 95.9 84.3 87.8 5 2_4_168_201_246 94.5 84.7 87.6 5 2_9_130_168_246 95.9 84.0 87.5 5 2_4_111_168_173 92.7 84.5 86.9 5 2_4_130_168_173 93.7 83.9 86.8 5 2_4_168_173_201 93.5 83.7 86.6 5 2_4_115_168_173 94.3 83.3 86.6 5 2_9_130_168_173 93.7 83.2 86.3 5 2_4_17_115_168 92.5 83.6 86.3 5 2_111_168_173_268 93.7 83.1 86.3 5 2_18_165_268_301 95.3 82.2 86.1 5 2_18_165_268_315 96.3 81.8 86.1 5 2_111_130_168_173 93.3 83.0 86.1 5 2_83_130_168_173 94.5 82.2 85.9 5 2_6_130_168_173 94.5 82.0 85.7 5 2_111_168_173_223 92.7 82.7 85.7 5 2_5_111_168_173 92.1 83.0 85.7 5 2_6_130_173_184 95.9 81.3 85.6 5 2_39_111_168_173 93.3 82.3 85.6 5 2_111_168_173_222 93.9 82.0 85.5 5 2_111_152_168_173 93.5 82.0 85.5 5 2_111_168_173_241 93.1 82.2 85.5 5 2_130_168_173_213 94.9 81.4 85.4 5 2_111_168_173_184 94.1 81.7 85.4 5 2_102_111_168_173 92.3 82.5 85.4 5 2_5_130_168_173 92.9 82.1 85.3 5 2_111_168_173_234 92.3 82.4 85.3 5 2_111_168_173_230 93.1 82.0 85.3 5 2_111_168_173_307 93.3 81.9 85.3 5 2_130_168_173_249 93.9 81.5 85.2 5 2_111_158_168_173 92.9 81.8 85.1 5 2_39_168_169_173 93.3 81.5 85.1

(973) TABLE-US-00012 TABLE 7-5 Combined Validation cohort gene number SEQ ID NO: Sensitivity Specificity Accuracy 3 9_165_168 95.9 83.0 86.9 4 9_165_168_173 96.5 83.2 87.2 4 9_128_165_168 95.3 83.6 87.1 4 9_17_165_168 94.7 83.5 86.9 4 9_80_165_168 97.4 82.2 86.8 4 2_9_168_246 93.3 82.1 85.5 5 5_9_165_168_173 96.5 83.9 87.6 5 9_128_129_165_168 94.5 84.6 87.5 5 2_9_130_168_246 95.9 84.0 87.5 5 9_17_159_165_168 94.7 83.4 86.8 5 9_17_165_168_173 95.1 83.1 86.7 5 2_9_130_168_173 93.7 83.2 86.3

(974) TABLE-US-00013 TABLE 7-6 Combined Validation cohort gene number SEQ ID NO: Sensitivity Specificity Accuracy 3 17_164_168 97.8 80.4 85.6 4 4_17_165_168 95.1 84.2 87.5 4 9_17_165_168 94.7 83.5 86.9 4 4_17_115_168 92.1 83.3 85.9 4 4_17_115_302 89.8 84.1 85.8 4 4_17_115_184 91.5 82.7 85.3 5 4_17_165_168_173 96.5 84.1 87.8 5 4_17_165_168_223 95.7 84.5 87.8 5 4_17_128_165_168 95.5 84.4 87.7 5 4_17_165_168_169 95.3 84.5 87.7 5 4_17_117_165_168 95.3 84.4 87.6 5 4_17_165_168_323 95.3 84.3 87.6 5 4_17_81_165_168 94.7 84.6 87.6 5 4_17_165_168_253 95.1 84.4 87.6 5 4_17_162_165_168 95.5 84.2 87.6 5 4_17_141_165_168 94.7 84.5 87.5 5 4_17_129_165_168 94.3 84.6 87.5 5 4_17_165_168_258 94.7 84.4 87.5 5 4_17_165_168_190 95.7 84.0 87.5 5 4_17_115_168_177 92.7 85.3 87.5 5 4_17_165_168_191 94.9 84.2 87.4 5 4_17_158_165_168 95.3 84.1 87.4 5 4_17_165_168_184 95.7 83.9 87.4 5 4_17_94_165_168 95.3 84.1 87.4 5 4_17_165_168_296 95.5 83.9 87.4 5 4_17_165_168_307 95.1 84.1 87.4 5 4_17_123_165_168 95.5 83.9 87.4 5 4_17_39_165_168 94.9 84.1 87.4 5 4_17_145_165_168 95.3 83.9 87.3 5 4_17_165_168_286 94.9 84.1 87.3 5 4_17_73_165_168 95.3 83.8 87.2 5 4_17_115_165_168 94.9 84.0 87.2 5 4_17_108_165_168 94.7 84.1 87.2 5 4_17_156_165_168 94.9 84.0 87.2 5 4_17_165_168_249 95.5 83.6 87.2 5 4_17_131_165_168 95.3 83.7 87.2 5 4_17_165_168_304 94.9 83.9 87.2 5 4_17_157_165_168 95.1 83.8 87.2 5 4_17_165_168_318 94.9 83.8 87.1 5 4_17_74_165_168 94.3 84.1 87.1 5 4_17_165_168_216 94.9 83.6 87.0 5 4_17_165_168_309 94.5 83.8 87.0 5 4_17_165_168_236 94.7 83.7 87.0 5 4_17_165_168_324 95.3 83.5 87.0 5 9_17_159_165_168 94.7 83.4 86.8 5 4_17_115_130_168 92.7 84.3 86.8 5 4_17_111_115_168 91.9 84.6 86.8 5 9_17_165_168_173 95.1 83.1 86.7 5 4_17_115_160_168 92.1 84.3 86.6 5 4_17_115_168_246 94.1 83.5 86.6 5 4_17_115_168_201 92.3 84.1 86.5 5 4_17_115_168_217 92.9 83.8 86.5 5 2_4_17_115_168 92.5 83.6 86.3 5 4_17_115_140_168 90.9 84.1 86.1 5 4_17_102_115_168 92.1 83.3 85.9

(975) TABLE-US-00014 TABLE 7-7 Combined Validation cohort gene number SEQIDNO: Sensitivity Specificity Accuracy 3 121_130_164 97.6 82.3 86.9 3 18_121_164 98.6 81.6 86.7 3 121_164_168 97.8 80.9 85.9 3 121_164_328 96.3 81.1 85.6 3 121_164_211 97.6 80.2 85.4 3 95_121_164 98.4 79.7 85.3 3 6_121_165 96.3 80.3 85.1 4 18_121_130_164 98.6 84.4 88.6 4 18_121_164_255 98.0 84.2 88.4 4 18_121_164_201 98.2 83.0 87.6 4 18_121_151_164 98.2 83.1 87.6 4 18_95_121_164 99.0 81.5 86.8 4 18_107_121_164 98.6 81.6 86.7 4 2_121_165_168 95.3 82.5 86.3 4 18_121_149_165 97.1 81.7 86.3 4 13_18_121_165 99.2 80.4 86.1 5 18_121_130_136_164 98.6 84.6 88.8 5 18_121_130_164_314 98.4 84.6 88.8 5 18_114_121_130_164 99.0 84.3 88.7 5 18_121_130_164_214 98.6 84.5 88.7 5 18_121_130_164_193 98.8 84.3 88.6 5 18_121_130_164_320 98.6 84.4 88.6 5 18_121_130_164_301 98.6 84.3 88.6 5 18_121_130_144_164 98.6 84.4 88.6 5 18_121_130_164_168 98.4 84.5 88.6 5 18_121_130_164_205 98.4 84.4 88.6 5 18_121_130_158_164 98.8 84.1 88.5 5 18_121_130_164_260 98.8 84.1 88.5 5 18_106_121_130_164 98.8 84.1 88.5 5 18_121_130_164_318 98.6 84.2 88.5 5 18_121_130_164_286 98.6 84.1 88.5 5 18_121_130_164_315 98.6 84.2 88.5 5 18_121_130_164_237 98.6 84.2 88.5 5 18_121_130_164_184 98.6 84.2 88.5 5 18_121_130_164_270 98.4 84.2 88.5 5 18_121_130_164_309 98.4 84.2 88.5 5 18_121_130_164_278 98.4 84.3 88.5 5 18_82_121_130_164 98.4 84.2 88.5 5 18_23_121_130_164 98.4 84.2 88.5 5 18_121_130_164_189 98.4 84.3 88.5 5 18_121_130_152_164 98.2 84.3 88.5 5 18_121_130_164_213 98.2 84.3 88.5 5 18_121_130_164_229 98.2 84.3 88.5 5 18_57_121_130_164 98.2 84.4 88.5 5 18_121_130_142_164 98.8 83.9 88.4 5 18_121_130_155_164 98.6 84.0 88.4 5 18_39_121_130_164 98.4 84.1 88.4 5 18_33_121_130_164 98.4 84.1 88.4 5 18_121_126_130_164 98.4 84.1 88.4 5 18_121_130_164_319 98.4 84.1 88.4 5 18_22_121_130_164 98.2 84.1 88.4 5 18_59_121_130_164 98.2 84.1 88.4 5 18_27_121_130_164 97.8 84.4 88.4 5 18_121_130_164_201 98.2 84.1 88.3 5 18_19_121_130_164 98.4 83.9 88.2 5 18_95_121_164_188 99.0 83.0 87.8 5 13_18_121_130_165 98.4 82.5 87.2

Example 3

(976) <Comparison of miRNA Expression Levels in Serum Between Lung Cancer Patient and Healthy Subject>

(977) In this Example, miRNA expression levels in sera were compared between lung cancer patients and healthy subjects in order to verify the reliability of the gene markers obtained in Examples 1 and 2. In this experiment, because higher statistical reliability regarding gene expression levels could be obtained when a larger number of samples is used, all the samples in which the gene expression levels were measured in the preceding Reference Examples were used (Table 11a). To be more specific, firstly, the miRNA expression levels of 1,694 lung cancer patients and 4,660 healthy subjects obtained in the preceding Reference Examples were combined and normalized by global normalization. Secondly, in order to evaluate diagnostic markers with higher reliability, only genes having the expression level of 2.sup.6 or higher in 50% or more of the samples in either of the lung cancer patient group or the healthy subject group, were selected. Thirdly, in order to evaluate a gene whose expression level significantly differs in statistics between a lung cancer patient group and the healthy subject group, a two-sided t-test assuming equal variance was carried out, and then, a P value after the Bonferroni correction was calculated. Forthly, in order to evaluate whether to be easily affected by noise at the time of measurement, an absolute value of the difference (fold change) in gene expression level, which is obtained by logarithmic conversion between the lung cancer patient group and the healthy subject group, was calculated. Genes having a P value after the correction which was 0.05 or less and having an absolute value of fold change which was 0.5 or more, were extracted as genes varying in expression. The results are shown in Table 8.

(978) TABLE-US-00015 TABLE 8 P value after Fold change of Bonferroni lung cancer patient to SEQ ID NO: correction healthy subject 1  <1E−308 2.02 2  <1E−308 2.95 3  <1E−308 1.63 7  <1E−308 0.81 10  5.30E−284 0.67 12  <1E−308 2.04 13  <1E−308 7.81 14  4.44E−148 −0.52 15  <1E−308 1.00 16  <1E−308 1.41 17  <1E−308 0.86 18  <1E−308 0.85 19  4.47E−85 0.65 20  <1E−308 1.29 21  <1E−308 1.85 22  <1E−308 3.64 23  <1E−308 1.60 25  <1E−308 3.01 26  <1E−308 1.87 27  <1E−308 3.01 29  <1E−308 1.91 30  <1E−308 4.83 31  <1E−308 3.23 33  <1E−308 1.53 34  3.29E−303 0.82 35  <1E−308 −0.54 36  2.02E−291 0.99 37  <1E−308 1.21 38  <1E−308 1.53 40  <1E−308 3.15 42  <1E−308 −0.94 43  <1E−308 2.13 44  <1E−308 1.95 45  <1E−308 2.38 46  <1E−308 0.58 47  <1E−308 1.30 50  <1E−308 4.63 51  <1E−308 1.09 55  <1E−308 0.68 56  <1E−308 1.19 57  <1E−308 3.71 58  <1E−308 −0.92 59  <1E−308 1.27 60  <1E−308 3.87 64  <1E−308 4.03 65  <1E−308 0.58 66  <1E−308 1.62 67  <1E−308 0.60 68  <1E−308 3.95 69  <1E−308 3.20 70  <1E−308 4.36 71  <1E−308 0.81 72  <1E−308 3.83 73  <1E−308 −2.42 74  <1E−308 0.97 75  <1E−308 3.76 76  <1E−308 1.16 78  <1E−308 4.29 79  7.77E−294 0.77 80  <1E−308 2.72 81  <1E−308 1.08 84  <1E−308 −0.80 85  <1E−308 3.89 86  4.63E−209 0.57 87  <1E−308 3.01 90  <1E−308 0.67 92  <1E−308 0.86 94  <1E−308 2.29 95  <1E−308 0.75 96  <1E−308 3.61 97  <1E−308 1.15 98  <1E−308 3.35 99  <1E−308 1.22 101  <1E−308 0.87 102  <1E−308 0.58 103  <1E−308 0.85 104  <1E−308 0.78 105  <1E−308 0.75 106  <1E−308 1.77 107  <1E−308 1.61 109  <1E−308 −0.58 110  <1E−308 0.89 111  <1E−308 0.72 113  8.52E−107 0.52 114  3.97E−267 0.63 115  <1E−308 1.51 118  <1E−308 −0.80 120  <1E−308 1.56 122  <1E−308 2.26 124  <1E−308 1.24 127  <1E−308 1.40 128  <1E−308 1.05 130  <1E−308 0.55 131  <1E−308 −1.09 134  <1E−308 1.38 135  <1E−308 3.67 136  <1E−308 −1.41 137  <1E−308 2.98 138  9.35E−164 0.54 140  8.27E−232 0.63 142  7.60E−293 0.73 143  <1E−308 2.39 144  <1E−308 1.12 145  <1E−308 −1.21 148  <1E−308 1.55 149  <1E−308 3.33 150  <1E−308 4.64 153  <1E−308 2.85 159  <1E−308 1.19 162  <1E−308 2.23 163  <1E−308 3.49 164  <1E−308 3.66 165  <1E−308 1.98 166  3.76E−62 −0.65 167  2.34E−248 0.61 170  <1E−308 4.76 172  <1E−308 1.30 173  <1E−308 1.13 175  <1E−308 −1.26 177  <1E−308 1.68 179  <1E−308 1.49 180  <1E−308 0.90 181  <1E−308 1.16 182  <1E−308 2.32 183  <1E−308 −0.85 184  <1E−308 −0.69 185  <1E−308 1.96 186  <1E−308 −0.95 187  <1E−308 1.14 188  <1E−308 4.99 190  <1E−308 4.22 193  <1E−308 0.65 195  <1E−308 5.97 196  <1E−308 4.90 197  <1E−308 5.16 198  <1E−308 3.04 199  <1E−308 2.28 200  <1E−308 0.74 201  <1E−308 1.42 202  <1E−308 0.72 206  <1E−308 2.54 207  <1E−308 2.68 209  <1E−308 1.03 211  <1E−308 1.06 214  <1E−308 1.09 215  <1E−308 −1.12 217  <1E−308 1.32 220  <1E−308 2.71 221  <1E−308 0.79 222  <1E−308 0.64 225  <1E−308 3.19 226  <1E−308 3.05 229  4.55E−203 −0.63 231  <1E−308 5.80 232  <1E−308 1.10 235  7.77E−196 −0.55 236  <1E−308 1.52 239  <1E−308 0.95 246  <1E−308 1.36 247  <1E−308 1.17 249  3.06E−90 −0.65 250  <1E−308 0.81 251  <1E−308 1.01 255  <1E−308 3.10 256  3.79E−269 0.56 257  <1E−308 1.99 259  <1E−308 1.72 260  <1E−308 3.26 261  <1E−308 1.88 262  <1E−308 1.54 263  <1E−308 3.49 265  2.97E−266 0.55 267  <1E−308 0.91 268  1.19E−234 0.55 269  <1E−308 0.77 272  <1E−308 1.43 273  1.04E−304 0.57 274  <1E−308 −0.92 276  <1E−308 0.73 277  6.62E−218 0.64 278  <1E−308 −1.41 279  <1E−308 −0.83 280  1.54E−225 0.57 281  <1E−308 1.05 282  <1E−308 −0.50 284  2.35E−278 −0.60 285  <1E−308 1.67 286  <1E−308 −1.27 287  <1E−308 1.31 290  <1E−308 1.08 291  <1E−308 1.57 293  <1E−308 −0.51 294  2.90E−300 0.64 295  <1E−308 1.12 296  5.92E−276 −0.64 297  6.60E−269 −0.60 298  <1E−308 0.87 299  <1E−308 2.46 300  <1E−308 2.52 301  <1E−308 0.87 303  <1E−308 0.88 304  <1E−308 −1.68 305  <1E−308 0.87 306  <1E−308 1.06 307  <1E−308 0.79 309  <1E−308 3.01 311  <1E−308 5.07 312  <1E−308 4.83 313  <1E−308 1.14 314  <1E−308 0.75 315  <1E−308 2.69 316  <1E−308 1.63 317  <1E−308 0.97 318  <1E−308 3.19 319  <1E−308 5.62 320  <1E−308 1.02 321  <1E−308 1.24 322  <1E−308 2.07 324  <1E−308 −1.84 327  5.87E−261 1.52 328  <1E−308 2.66 329  <1E−308 3.30

Example 4

(979) <Comparison of miRNA Expression Levels in Serum Between Lung Cancer Patient and Benign Bone and Soft Tissue Tumor Patients and Benign Breast Disease Patients>

(980) In this Example, miRNA expression levels in sera were compared between lung cancer patients and benign bone and soft tissue tumor patients and benign breast disease patients in order to verify the reliability of the gene markers obtained in Examples 1 and 2. In this experiment, because higher statistical reliability regarding gene expression levels could be obtained when a larger number of samples is used, all the samples in which the gene expression levels were measured in the preceding Reference Examples were used (Table 11a). To be more specific, firstly, the miRNA expression levels of 1,694 lung cancer patients and 368 benign bone and soft tissue tumor patients and benign breast disease patients obtained in the preceding Reference Examples were combined and normalized by global normalization.

(981) Secondly, in order to evaluate diagnostic markers with higher reliability, only genes having the expression level of 2.sup.6 or higher in 50% or more of the samples in either of the group of lung cancer patients or the group of benign bone and soft tissue tumor patients and benign breast disease patients, were selected. Thirdly, in order to evaluate a gene whose expression level significantly differs in statistics between the group of lung cancer patients and the group of benign bone and soft tissue tumor patients and benign breast disease patients, a two-sided t-test assuming equal variance was carried out, and then, a P value after the Bonferroni correction was calculated. Forthly, in order to evaluate whether to be easily affected by noise at the time of measurement, an absolute value of the difference (fold change) in gene expression level, which is obtained by logarithmic conversion between the group of lung cancer patients and the group of benign bone and soft tissue tumor patients and benign breast disease patients, was calculated. A gene having a P value after the correction which was 0.05 or less and having an absolute value of fold change which was 0.5 or more, was extracted as a gene varying in expression. The results are shown in Table 9.

(982) TABLE-US-00016 TABLE 9 Fold change of lung cancer patient to benign bone and soft P value after tissue tumor patients Bonferroni and benign SEQ ID NO: correction breast disease patients 1  2.39E−129 0.94 2  1.31E−199 2.34 3  7.47E−167 1.49 4  3.64E−68 −1.48 8  2.49E−75 1.03 9  9.04E−40 −1.17 11  8.51E−43 −0.55 12  7.12E−163 1.24 13  1.57E−149 2.56 15  1.26E−108 1.26 20  5.02E−73 1.03 22  2.96E−67 1.33 23  2.55E−128 1.57 24  7.59E−83 −0.55 25  1.04E−58 1.12 27  1.98E−75 1.76 29  2.82E−175 1.91 30  2.35E−57 1.78 31  9.31E−74 1.14 32  3.51E−288 −0.51 33  2.39E−102 1.50 34  1.65E−117 0.87 36  2.38E−48 0.85 40  7.11E−197 2.24 43  4.45E−73 0.88 44  6.93E−34 0.88 45  1.20E−84 0.83 47  2.20E−55 0.84 48  7.93E−64 0.79 50  4.47E−86 1.69 56  6.73E−93 0.90 57  6.51E−65 1.24 59  1.22E−39 0.85 60  6.33E−158 2.26 64  8.48E−18 1.00 66  1.35E−144 0.77 68  4.04E−101 1.61 69  1.85E−27 1.00 70  5.91E−114 1.85 72  1.62E−91 1.67 73  2.55E−32 0.62 75  2.81E−85 1.55 76  4.11E−23 0.59 78  2.75E−73 1.79 79  1.95E−45 0.85 80  1.21E−150 1.33 85   <1E−308 4.19 87  2.13E−115 1.66 94  7.34E−131 1.46 96  8.87E−95 1.42 98  4.83E−171 2.02 99  1.02E−39 0.84 102  6.67E−165 1.11 106  5.24E−29 0.50 107  7.47E−61 0.67 110  5.98E−82 0.53 114  2.73E−20 0.52 115  8.65E−115 0.54 120  3.91E−46 0.81 122  4.73E−52 1.17 126  1.19E−154 −0.53 128  9.40E−33 0.64 134  1.36E−41 0.72 135  5.46E−172 2.32 136  4.38E−35 −0.70 137  <1E−308 1.71 138  9.15E−27 0.64 139  9.22E−34 0.62 140  1.08E−44 0.74 143  2.03E−70 1.52 144  3.76E−22 0.62 148  1.34E−47 0.66 149  8.40E−110 1.76 150  1.98E−89 1.68 153  1.39E−161 2.04 159  1.11E−50 0.74 163  1.05E−120 1.98 164  <1E−308 2.51 165  9.44E−220 1.28 166  5.85E−66 −1.73 167  6.22E−235 1.31 170  7.90E−67 1.84 172  2.04E−94 1.31 173  9.00E−61 0.60 179  5.55E−45 0.55 181  7.23E−54 0.81 182  1.03E−104 0.81 185  1.24E−82 1.06 186  8.97E−59 0.86 188  <1E−308 6.00 189  6.66E−102 1.18 190  2.48E−177 2.08 194  3.50E−122 0.67 195  6.34E−123 1.89 196  1.24E−104 2.05 197  5.84E−97 2.35 198  1.14E−114 1.54 199  8.95E−90 0.93 201  1.58E−195 1.24 202  6.22E−55 0.58 206  2.35E−30 0.56 209  2.52E−75 0.52 213  1.88E−68 −0.66 217  3.25E−133 0.94 220  2.19E−173 1.30 225  4.62E−84 1.58 226  8.00E−184 1.32 228  1.25E−59 1.42 231  <1E−308 4.03 235  2.68E−20 0.52 241  2.57E−182 −0.57 244  1.26E−14 0.53 249  2.46E−25 −0.78 250  2.66E−89 0.58 255  8.95E−34 0.58 257  5.57E−54 1.34 260  4.52E−157 1.97 262  3.71E−31 0.53 263  4.51E−89 1.03 285  6.31E−83 1.16 287  2.36E−295 1.36 289  5.59E−114 1.04 291  4.37E−44 0.55 294  2.77E−20 0.51 299  6.64E−135 1.05 303  7.57E−59 0.95 311  2.95E−83 2.16 312  3.35E−238 2.89 313  1.44E−53 0.76 315  1.73E−20 0.68 319  7.52E−85 1.75 320  3.60E−29 0.71 322  9.40E−116 1.07 325  3.44E−130 −0.55 327  2.41E−29 0.90 328  2.19E−125 1.08 329  2.60E−73 1.31

Example 5

(983) <Comparison of miRNA Expression Levels in Serum Between Lung Cancer Patient and Patient Having a Cancer Other than Lung Cancer>

(984) In this Example, miRNA expression levels in sera were compared between lung cancer patients and other cancer patients in order to verify the reliability of the gene markers obtained in Examples 1 and 2. In this experiment, because higher statistical reliability regarding gene expression levels could be obtained when a larger number of samples is used, all the samples in which the gene expression levels were measured in the preceding Reference Examples, were used (Table 11a). To be specific, firstly, the miRNA expression levels of 1,694 lung cancer patients and 4,147 other cancer patients obtained in the preceding Reference Examples were combined and normalized by global normalization. Secondly, in order to evaluate diagnostic markers with higher reliability, only genes having the expression level of 2.sup.6 or higher in 50% or more of the samples in either of the group of lung cancer patients or the group of other cancer patients, were selected. Thirdly, in order to evaluate a gene whose gene expression level significantly differs in statistics between the group of lung cancer patients and the group of other cancer patients, a two-sided t-test assuming equal variance was carried out, and then, a P value after the Bonferroni correction was calculated. Forthly, in order to evaluate whether to be easily affected by noise at the time of measurement, an absolute value of the difference (fold change) in gene expression level, which is obtained by logarithmic conversion between the group of lung cancer patients and the group of patients having a cancer other than lung cancer, was calculated. A gene having a P value after the correction which was 0.05 or less and having an absolute value of fold change which was 0.5 or more, was extracted as a gene varying in expression. The results are shown in Table 10.

(985) TABLE-US-00017 TABLE 10 Fold change of P value after lung cancer patient to Bonferroni patient having cancer SEQ ID NO: correction other than lung cancer 1 4.58E−123 0.55 2 1.88E−145 1.27 3 6.31E−96 0.66 4 1.76E−150 −1.08 9 8.54E−95 −0.93 13 1.21E−114 1.38 20 1.20E−69 0.57 23 2.52E−48 0.53 29 3.77E−99 0.77 30 3.12E−43 0.83 33 1.61E−53 0.57 40 8.43E−82 0.78 50 2.76E−40 0.67 60 7.34E−122 1.10 64 4.67E−30 0.64 68 4.99E−91 0.92 69 9.36E−39 0.58 70 8.65E−59 0.77 72 5.35E−106 0.91 75 2.31E−52 0.67 78 3.67E−39 0.73 87 6.09E−57 0.66 94 1.00E−113 0.90 96 3.83E−68 0.65 98 6.51E−115 0.93 102 4.09E−92 0.51 120 2.93E−63 0.61 122 5.74E−73 0.76 135 2.97E−118 1.08 140 1.69E−67 0.56 143 1.34E−60 0.74 149 8.83E−80 0.88 150 2.47E−76 0.89 153 3.64E−76 0.80 163 1.53E−95 0.91 164 5.78E−212 0.92 165 2.37E−104 0.56 166 2.06E−83 −1.03 170 9.80E−60 0.85 188 1.53E−44 0.57 195 1.39E−75 0.83 196 5.59E−82 1.00 197 1.10E−77 1.09 198 1.49E−75 0.74 220 6.63E−89 0.56 225 3.64E−51 0.67 228 1.25E−100 0.86 231 2.36E−114 1.27 260 8.14E−106 0.92 263 6.10E−65 0.66 311 6.14E−102 1.34 312 9.19E−63 0.80 319 4.08E−58 0.97 327 4.54E−51 0.69 329 4.55E−101 0.92

(986) As shown in the above Examples, the kit, device and method of the present invention can detect lung adenocarcinoma, lung squamous cell carcinoma, large cell lung carcinoma, small cell lung carcinoma and other lung cancers with higher sensitivity than the existing tumor markers and therefore permit early detection of lung cancer. As a result, a treatment such as a chemotherapy, a radiotherapy, an immunotherapy, a molecular targeted therapy, or surgery with a high degree of probability for complete therapy can be applied early, thereby significantly improving a survival rate.

INDUSTRIAL APPLICABILITY

(987) According to the present invention, various histological types or stages of progression of lung cancer can be effectively detected by a simple and inexpensive method. This enables early detection, diagnosis and treatment of lung cancer. Also, the method of the present invention enables less-invasive detection of lung cancer using patient's blood and therefore lung cancer can be simply and quickly detected.

(988) All publications, patents, and patent applications cited herein are incorporated herein by reference in their entirety.