The present invention relates to a biomarker composition for diagnosing and predicting prognosis of prostate cancer, and that the detection rate and expression level of gene combination composed with AR (Androgen receptor), AR-V7 (Androgen receptor variant 7), EpCAM (Epithelial cell adhesion molecule) in blood tumor cells (CTC) isolated from patients, Epithelial cell adhesion molecule), KRT-19 (Cytokeratin 19), PSA (Prostate specific antigen), and PSMA (Prostate specific membrane antigen) in circulating tumor cells (CTCs) isolated from patients is related to the level of malignancy in prostate cancer is confirmed and thus the gene combination provides as a biomarker for prostate cancer diagnosis and a biomarker for prognosis prediction of prostate cancer.

The disclosure provides a method of predicting de novo resistance to androgen receptor (AR) targeted therapy in a tumor of a prostate cancer patient comprising (a) performing a direct analysis comprising immunofluorescent staining and morphological characteristization of nucleated cells in a blood sample obtained from the patient to generate circulating tumor cell (CTC) data, wherein the analysis comprises determining a measurable feature of a panel of traditional and non-traditional CTC biomarkers for de novo resistance to androgen receptor (AR) targeted therapy, and (c) evaluating the CTC data to determine the probability of de novo resistance to the AR targeted therapy in the tumor of the prostate cancer patient. In some embodiments, the immunofluorescent staining comprises staining of nucleated cells comprises pan cytokeratin, cluster of differentiation (CD) 45, diamidino-2-phenylindole (DAPI) and AR. In some embodiments, the biomarkers comprise (1) CTC heterogeneity, (2) frequency of cytokeratin positive (CK+), androgen receptor positive (AR+), nucleoli positive (nucleoli+) CTCs, and (3) frequency of C-terminal truncated CTCs. The method of claim 3, wherein the CTC heterogeneity further comprises biomarkers selected from the group consisting of traditional CTCs, CTC clusters, CK− CTCs, small CTCs, nucleoli.sup.+CTCs, CK speckled CTCs and the biomarkers listed in Table 1.

The disclosure provides a method of predicting resistance to androgen receptor (AR) targeted therapy in a prostate cancer patient comprising (a) performing a direct analysis comprising immunofluorescent staining and morphological characterization of nucleated cells in a blood sample obtained from the patient to identify circulating tumor cells (CTCs), and (b) based on said direct analysis further determining the presence of a biomarker signature that is predictive of resistance to AR targeted therapy in the prostate cancer patient, wherein the biomarker signature comprises CK+, AR+, nucleoli+ CTCs in a subpopulation of said CTCs. The present disclosure also provides a method of predicting resistance to taxane-based chemotherapy in a prostate cancer patient comprising (a) performing a direct analysis comprising immunofluorescent staining and morphological characterization of nucleated cells in a blood sample obtained from the patient to identify circulating tumor cells (CTCs), and (b) based on said direct analysis further determining the presence of a biomarker signature that is predictive of resistance to taxane-based chemotherapy in the prostate cancer patient, wherein the biomarker signature comprises CK+, AR−, nucleoli+, small size in a subpopulation of said CTCs.

Methods are provided for assaying bladder-associated samples. Aspects of the methods include detecting per cell programmed-death ligand 1 (PD-L1) expression in a bladder-associated sample. In some instances, the methods include detecting whether an immune cell that expresses PD-Ll above a predetermined threshold is present in a bladder-associated sample and/or detecting a PD-L1-aneuploid-to-PD-L1-epithelial ratio of a bladder-associated sample. Aspects of the methods may also include identifying whether a malignant bladder-associated neoplasia is present. Methods are also provided for treating a subject for a malignant bladder-associated neoplasia, wherein aspects of such methods include administering a therapeutic to a subject having an identified malignant bladder-associated neoplasia. In addition, kits that find use in practicing the subject methods are also provided.

Disclosed herein are antibodies having binding specificity to the amino acid sequences Ala Ser Ser Gly Leu Thr Val Glu Val Asp (SEQ ID NO:1) and Thr Val Glu Val Asp (SEQ ID NO:14), and methods of detecting cell death in a sample, comprising contacting the sample with a first antibody specific for a C-terminal amino acid sequence Ala Ser Ser Gly Leu Thr Val Glu Val Asp (SEQ ID NO:1) or Thr Val Glu Val Asp (SEQ ID NO:14) of a CK18 protein fragment having a C-terminal amino acid sequence of Val Glu Val Asp (SEQ ID NO:2) and a second antibody that specifically binds an epitope that is present in both full-length CK18 and the CK18 protein fragment, and that does not overlap with SEQ ID NO:1 or SEQ ID NO:14, under conditions such that the CK18 protein fragment present in the sample specifically binds to the first antibody and the second antibody, wherein one of the antibodies is bound to a solid support and the other antibody is bound to a detection moiety capable of producing a signal; optionally removing any unbound or excess material; and detecting the signal from the detection moiety, wherein the signal is positively correlated with the presence of the CK18 protein fragment in the sample.

The present invention provides a method for determining the prognosis of cancer in a subject. The method comprises measuring the amount of megakaryocytes in a sample from the subject. Usually, the sample is a blood sample. The method may also comprise measuring the number of circulating tumour cells (CTCs) in the sample, and in some embodiments a comparison of the number of megakaryocytes and CTCs in the sample. The present invention also provides methods of treatment for cancer in a patient for whom a poor prognosis is predicted using a method of prognosis of the invention.

This disclosure describes methods, kits, and systems for scoring the immune response to cancer through examination of tissue infiltrating lymphocytes (TILs). Methods of scoring the immune response in cancer using tissue infiltrating lymphocytes include detecting CD3, CD8, CD20, and FoxP3 within the sample and scoring the detection manually or scoring the digital images of the staining with the aid of image analysis and algorithms.

Disclosed are a biomarker, method and assay kit for identifying and screening for urothelial carcinoma (UC) in a subject in need.

This disclosure describes methods, kits, and systems for scoring the immune response to cancer through examination of tissue infiltrating lymphocytes (TILs). Methods of scoring the immune response in cancer using tissue infiltrating lymphocytes include detecting CD3, CD8, CD20, and FoxP3 within the sample and scoring the detection manually or scoring the digital images of the staining with the aid of image analysis and algorithms.

A nanowires/microscale pyramids (NWs/MPs) substrate complex structure is formed with a plurality of pyramids. Each triangular surface of the pyramid is formed with nanowires to increase the contact area. In one application, anti-epithelial-cell adhesion-molecule (anti-EpCAM) antibodies are modified on the nanowires. The anti-EpCAM antibodies serve to capture circulating tumor cells (CTCs) in blood for determining whether the cancer cells have metastasized to other organs. In another application, the nanowires are modified with silver nanoparticles (AgNPs) which can be combined with other functional groups for testing. The AgNPs on the NWs/MPs substrate causes the NWs/MPs substrate to become a substrate with surface enhanced Raman scattering (SERS). The AgNPs are bound with Epstein-Barr virus (EBV) probe DNA which can be hybridized with EBV target DNAs so as to determine the concentration of the EBV target DNAs in blood. The methods for fabricating the substrate and its applications are also provided.