Means and Methods for Diagnosing Pancreatic Cancer in a Subject Based on a Biomarker Panel

Abstract

The present invention relates to a method for diagnosing pancreatic cancer in a subject comprising the steps of: (a) determining in at least one sample of said subject the amounts of a group of diagnostic biomarkers comprising (i) at least one diagnostic amino acid, said diagnostic amino acid being proline, histidine or tryptophan, preferably, being proline; (ii) at least one diagnostic ceramide, said diagnostic ceramide being ceramide (d18:1,C24:0) or ceramide (d18:2,C24:0), preferably being ceramide (d18:1,C24:0); (iii) at least one diagnostic sphingomyelin, said diagnostic sphingomyelin being sphingomyelin (35:1), sphingomyelin (d17:1,C16:0), sphingomyelin (41:2) or sphingomyelin (d18:2,C17:0), preferably being sphingomyelin (35:1); and (iv) CA19-9; and (b) comparing said amounts of the diagnostic biomarkers with a reference, whereby pancreatic cancer is diagnosed. Moreover, the present invention relates to a method for determining the probability for a subject to suffer from pancreatic cancer, and to devices and uses related to said methods.

Claims

1. A method for diagnosing pancreatic cancer in a subject comprising the steps of: (a) determining in at least one sample of said subject the amounts of a group of diagnostic biomarkers comprising (i) at least one diagnostic amino acid, said diagnostic amino acid being proline, histidine or tryptophan; (ii) at least one diagnostic ceramide, said diagnostic ceramide being ceramide (d18:1,C24:0) or ceramide (d18:2,C24:0) (iii) at least one diagnostic sphingomyelin, said diagnostic sphingomyelin being sphingomyelin (35:1), sphingomyelin (d17:1,C16:0), sphingomyelin (41:2) or sphingomyelin (d18:2,C17:0); and (iv) CA19-9; and (b) comparing said amounts of the diagnostic biomarkers with a reference, whereby pancreatic cancer is diagnosed, wherein said subject is a subject at least 40 years old.

2. The method of claim 1, wherein said subject is a subject at risk of suffering from pancreatic cancer and/or a subject suffering from chronic pancreatitis; or wherein said subject is a subject suspected to suffer from pancreatic cancer.

3. The method of claim 1, wherein said subject is a subject with a low CA19-9 value.

4. The method of claim 1, wherein said pancreatic cancer is a pancreatic cancer with a resectable tumor stage.

5. The method of claim 1, wherein (i) said diagnostic amino acid is proline; (ii) said diagnostic ceramide is ceramide (d18:1,C24:0) or ceramide (d18:2,C24:0); and/or (iii) said diagnostic sphingomyelin is sphingomyelin (35:1).

6. The method of claim 1, wherein said sphingomyelin (35:1) is the sum of sphingomyelin (d18:1,C17:0) and sphingomyelin (d17:1,C18:0); sphingomyelin (d18:1,C17:0); or sphingomyelin (d17:1,C18:0).

7. The method of claim 1, wherein said group of diagnostic biomarkers comprises, the diagnostic biomarkers proline, ceramide (d18:2,C24:0), sphingomyelin (35:1), and CA19-9.

8. The method of claim 1, wherein said group of diagnostic biomarkers further comprises at least one diagnostic ethanolamine lipid, said diagnostic ethanolamine lipid being phosphatidylethanolamine (C18:0,C22:6), lysophosphatidylethanolamine (C18:0), or lysophosphatidylethanolamine (C18:2).

9. The method of claim 1, wherein said group of diagnostic biomarkers comprises the diagnostic biomarkers CA19-9, Ceramide (d18:1,C24:0), Ceramide (d18:2,C24:0), Histidine, Lysophosphatidylethanolamine (C18:0), Lysophosphatidylethanolamine (C18:2), Phosphatidylethanolamine (C18:0,C22:6), Proline, Sphingomyelin (d17:1,C16:0), Sphingomyelin (35:1), Sphingomyelin (41:2), Sphingomyelin (d18:2,C17:0), and Tryptophan.

10. The method of claim 1, wherein said comparing amounts of diagnostic biomarkers with references comprises comparing said amounts or a value calculated therefrom to one or more cutoff values.

11. The method of claim 1, wherein said sample is a sample of a bodily fluid.

12. The method of claim 1, comprising the further step of separating said at least one diagnostic amino acid from said at least one diagnostic ceramide, said further step preceding step (a).

13. The method of claim 1, comprising the steps of (a) quantitatively determining the amounts of a group of diagnostic biomarkers in a sample of a subject, (b1) for each amount of (a), calculating a scaled amount by first subtracting a predetermined, diagnostic biomarker-specific subtrahend from said amount and then dividing the resulting value by a predetermined, diagnostic biomarker-specific divisor, (b2) calculating a prediction score by (i) assigning a diagnostic biomarker-specific weight value to each scaled amount of (b1), thereby providing a weighed amount, (ii) summing up said weighed amounts for all diagnostic biomarkers, providing a sum of weighted amounts, and (b3) determining the probability for a subject to suffer from pancreatic cancer based on the prediction score determined in step (b2).

14. The method of claim 1, wherein comparing said amounts of the diagnostic biomarkers with a reference comprises assigning a smaller weight, to the amount of CA19-9 in case the amount of CA19-9 determined is less than about 5 U/ml.

15. A diagnostic device for carrying out a method according to claim 1, comprising: a) an analysing unit comprising at least one detector for at least the small molecule diagnostic biomarkers of a group of diagnostic biomarkers according to claim 1, wherein said analyzing unit is adapted for determining the amounts of at least said small molecule diagnostic biomarkers detected by the at least one detector, and, operatively linked thereto; b) an evaluation unit comprising a computer comprising tangibly embedded a computer program code for carrying out a comparison of the determined amounts of the small molecule diagnostic biomarkers with a reference and a data base comprising said reference for said diagnostic biomarkers, whereby it is diagnosed whether a subject suffers from pancreatic cancer.

16. (canceled)

Description

FIGURE LEGENDS

[0193] FIG. 1: Legend to the graphical presentation of FIGS. 2 to 5.

[0194] FIG. 2: CA19-9 concentration (U/ml) in samples from patients suffering from various diseases: 1: Pancreatic cancer; 2: Chronic pancreatitis; 3: Non-pancreatic control (thyroid resections and hernia repair); 4: Diabetes and other comorbidities; 5: Other comorbidities, but no diabetes; 6: Small cell lung cancer; 7: Non-small cell lung cancer (NSCLC); 8: NSCLC adenocarcinoma; 9: NSCLC large cell carcinoma; 10: NSCLC squamous cell carcinoma; 11: Diabetes and dyslipidemia, most also hypertension; 12: Diabetes but no dyslipidemia, more than half also hypertension; 13: No comorbidities, age 62 or younger; 14: No comorbidities, age 63 or older; 15: Prostate cancer; 16: Cardiovascular diseases; 17: Chronic obstructive pulmonary disease, half also hypertension; 18: Dyslipidemia but no diabetes, more than half also hypertension; 19: Hypertension with other comorbidities, but no diabetes or dyslipidemia; 20: Hypertension only; 21: Other comorbidities, age 62 or younger; 22: Other comorbidities, age 63 or older; 23: Thyroid disorders. Graphical representation as described in FIG. 1.

[0195] FIG. 3: Prediction scores of panel 1 with (A) and without (B) CA19-9 for various diseases; graphical representation as described in FIG. 1, diseases as described in legend to FIG. 2.

[0196] FIG. 4: Prediction scores of panel 7 with (A) and without (B) CA19-9 for various diseases; graphical representation as described in FIG. 1, diseases as described in legend to FIG. 2.

[0197] FIG. 5: Prediction scores of panel 28 with (A) and without (B) CA19-9 for various diseases; graphical representation as described in FIG. 1, diseases as described in legend to FIG. 2.

EXAMPLE 1: PATIENT CHARACTERISTICS, PLASMA PREPARATION

[0198] A total of 235 patients with pancreatic cancer, chronic pancreatitis and non-pancreatic controls (hernia repair and thyroid resections) were enrolled in the clinical study. In this retrospective case control study, samples of 77 patients suffering from pancreatic ductal adenocarcinoma (PDAC) (40 of them in a resectable tumor stage (IA-IIB)), 79 samples of chronic pancreatitis (CP) patients, samples of 79 non-pancreatic control patients matched for age, gender and BMI were included. The mean age of the pancreatic cancer patients was 67 years. The mean age of the chronic pancreatitis patients was 51 years. The mean age of the non-pancreatic control patients was 64 years. Patients were overnight fasted and consecutively recruited from one clinical center. Exclusion criteria were a concomitant malignant disease, curative treatment of malignant disease less than 2 years of recruitment to the trial, concomitant cystic diseases of the pancreas, pregnancy or patients unable to give informed consent.

[0199] Additionally, plasma samples of 52 male diabetes patients and 52 male non-diabetic patients, age and BMI matched from five different centers, overnight fasted, were analyzed. The mean age of the diabetic patients was 69 years. The mean age of the non-diabetic patients was 69 years. All patients or their legal representatives gave their written informed consent and the local ethics review boards approved the protocol. After blood drawing and centrifugation according to the blood draw tube manufacturer's instruction, EDTA plasma was collected in Eppendorf tubes and stored at 80 C. for further analysis.

EXAMPLE 2: BIOMARKER ANALYSIS

[0200] The small molecule diagnostic biomarkers of the groups of diagnostic biomarkers listed as panels in Table 9 were analyzed by a one-shot LC-MS/MS measurement described in Example 3, where the analytes are further characterized by multiple reaction monitoring (MRM) transitions. Each analyte may contain more than one metabolite, whereby the metabolites contained in the same analyte have at least identical sum formula parameters and, thus, in the case of, e.g., lipids an identical chain length and identical numbers of double bonds in the fatty acid and/or other long-chain aliphatic moieties, e.g., sphingobase moieties.

[0201] Carbohydrate antigen 19-9 (CA 19-9) was analyzed in blood plasma or serum by a radioimmunoassay (RIA) in clinical chemistry laboratories. The normal range of CA 19-9 in the blood of a healthy individual is 0-37 U/mL (Units per milliliter).

EXAMPLE 3: ANALYTICAL METHOD

[0202] Human plasma samples were prepared and subjected to LC-MS/MS analysis as follows: 20 l human plasma was mixed with 100 l internal standard mixture (alanine d4: 12.24 g/ml; ceramide (d18:1,C17:0): 0.154 g/ml were dissolved in dimethyl sulfoxide, methanol, dichloromethane and water (in a ratio 12.3:2.2:1.1:1, v/v/v/v)) and 700 l extraction solvent containing methanol and dichloromethane in a ratio of 2:1 (v/v).

[0203] After the samples were thoroughly mixed at 20 C. for 5 min, the precipitated proteins were removed by centrifugation for 10 min. 150 l of the liquid supernatant was transferred to an appropriate glass vial for further derivatization with dansyl chloride, which allows the dansylation of primary and secondary amine groups. For this purpose, 25 l of 0.2 mol/l sodium bicarbonate buffer (dissolved in water), 25 l of 4 mg/ml dansyl chloride solution (dissolved in acetonitrile) and 50 l dimethyl sulfoxide were added. The dansylation was carried out under constant mixing at 35 C. for 150 min. The so-obtained reaction mixtures were analyzed by LC-MS/MS.

[0204] The LC-MS/MS systems consisted of an Agilent 1100 LC system (Agilent Technologies, Waldbronn, Germany) coupled with an API 4000 Mass spectrometer (ABSCIEX, Toronto, Canada). HPLC analysis was performed on commercially available reversed phase separation columns with C18 stationary phases (Phenomenex Ascentis Express C18, 2.7 m, 502.1 mm).

[0205] Up to 2 l of the above-mentioned so-obtained reaction mixture was injected and separated by gradient elution using a mixture of solvents consisting of methanol, water, formic acid, 2-propanol and 2-methoxy-2-methylpropane at a flow rate of 600 l/min (e.g. starting from 0% solvent B to 100% solvent B in 7 min):

Solvent A: 400 g methanol, 400 g water, 1 g formic acid
Solvent B: 400 g 2-methoxy-2-methylpropane, 200 g 2-propanol, 100 g methanol, 1 g formic acid

[0206] Mass spectrometry was carried out by electrospray ionization (ESI) in positive ion mode using multiple reaction monitoring (MRM). Using ESI, sphingomyelins with equal numbers of carbons and double bonds were detected together, these isobaric species were not separated chromatographically.

[0207] The diagnostic biomarkers listed in Table 1 can be measured with MRM. The respective amino acid analytes were measured with a quantifier and a qualifier MRM transition, whereas the analytes of the diagnostic biomarkers listed in Table 1 are measured with a respective quantifier only.

[0208] Quantitative evaluations of all small molecule biomarkers with commercially available quantification standards were achieved by external calibration in delipidized plasma. Delipidized plasma was used to simulate a matrix as close as possible to real plasma.

[0209] For small molecule biomarkers without commercially available standards, a commercially available standard of the same lipid class was used for the external calibration.

[0210] Reference controls were prepared by lyophilization of different amounts of commercially available human plasma (12 l, 20 l, 28 l) to check the linearity of small molecule biomarkers under real matrix condition. The ratios of the calculated concentrations of 12 l/20 l and 28 l/20 l of the lyophilized human reference control plasma delivered values between 0.5 and 0.7 and between 1.3 and 1.5, respectively, for all small molecule biomarkers of Table 1.

[0211] Recovery controls were prepared by adding a known standard concentration to lyophilized plasma samples of the same commercially available human reference control plasma as used for the reference controls. The lyophilized plasma samples were stored in a freezer until sample preparation.

[0212] Inter-day quality controls were prepared by extracting multiple samples of the commercially available human reference control plasma with extraction solvent and internal standard solution followed by dansylation. The dansylated reaction mixtures of all samples were pooled, and stored in aliquots in a freezer until they were used for the daily quality control of the instrument performance and sample preparation.

[0213] Quality controls for the method precision were prepared daily by extracting multiple samples of the commercially available human reference control plasma and were measured equally distributed in the sample batch.

TABLE-US-00001 TABLE 1 Diagnostic biomarkers used for generating groups of diagnostic biomarkers and their quantification and internal standards for analysis; for the diagnostic biomarkers sphingomyelin (35:1) and sphingomyelin (41:2), see text; the term direction refers to the direction of change of the respective diagnostic biomarker in samples from pancreatic cancer patients versus the non-pancreatic cancer samples of the study. Transition (parent/ Internal fragment) Quantification Standard Standard Diagnostic biomarker Direction (Da) Compound Compound Amino acids Histidine down 622.5/170.1 L-Histidine L-Alanine d4 Amino acids Proline down 349.3/170.1 L-Proline L-Alanine d4 Amino acids Tryptophan down 438.3/170.1 L-Tryptophan L-Alanine d4 Ceramides Ceramide (d18:1, C24:0) down 650.6/264.2 Ceramide (d18:1, C24:0) Ceramide (d18:1, 17:0) Ceramides Ceramide (d18:2, C24:0) down 648.6/262.2 Ceramide (d18:1, C24:1) Ceramide (d18:1, 17:0) Ethanolamine Lysophosphatidylethanolamine down 715.6/341.4 Lysophosphatidylethanolamine L-Alanine lipids (C18:0) (C18:0) d4 Ethanolamine Lysophosphatidylethanolamine down 711.6/337.4 Lysophosphatidylethanolamine L-Alanine lipids (C18:2) (C18:0) d4 Ethanolamine Phosphatidylethanolamine up 1025.8/651.6 Phosphatidylethanolamine L-Alanine lipids (C18:0, C22:6) (C18:0, C22:6) d4 Sphingomyelins Sphingomyelin (d17:1, C16:0) up 689.5/184.1 Sphingomyelin (d18:1, C17:0) Ceramide (d18:1, 17:0) Sphingomyelins Sphingomyelin (35:1) up 717.5/184.1 Sphingomyelin (d18:1, C17:0) Ceramide (d18:1, 17:0) Sphingomyelins Sphingomyelin (41:2) up 799.5/184.1 Sphingomyelin (d18:1, C24:1) Ceramide (d18:1, 17:0) Sphinomyelins Sphingomyelin (d18:2, C17:0) up 715.5/184.1 Sphingomyelin (d18:1, C17:0) Ceramide (d18:1, 17:0)

EXAMPLE 4: DATA ANALYSIS, NORMALIZATION AND STATISTICAL EVALUATION

[0214] For each diagnostic biomarker listed in Table 1, the direction of change in PDAC patients relative to controls consisting of CP patients and non-pancreatic controls was calculated by a simple linear model (ANOVA) with disease, age, gender, BMI, and sample storage time, if appropriate, as fixed effects. The direction Up means that the levels of the biomarker are higher in PDAC patients relative to controls consisting of CP patients or non-pancreatic controls, the direction Down means that the levels of the biomarker are lower in PDAC patients relative to CP patients or non-pancreatic controls. Prior to statistical analysis, log 10 transformation of ratios was conducted to assure normal distribution of data. The software R 2.8.1 (package nlme) was used for ANOVA.

[0215] The direction of change and ANOVA results of all small molecule biomarkers that were subsequently used for biomarker panel definition are given in the Tables 2 to 7, below:

TABLE-US-00002 TABLE 2 List of identified biomarkers in plasma for pancreatic cancer relative to chronic pancreatitis ANOVA result of pancreatic cancer relative to chronic pancreatitis Estimated fold Diagnostic biomarker change p-value t-value Sphingomyelin (35:1) 1.261 0.00023 3.749 Phosphatidylethanolamine 1.327 0.00705 2.719 (C18:0, C22:6) Lysophosphatidylethanolamine 0.879 0.05333 1.942 (C18:0)

TABLE-US-00003 TABLE 3 List of identified biomarkers in plasma for pancreatic cancer relative to non-pancreatic controls ANOVA result of pancreatic cancer relative to non-pancreatic controls Estimated fold Diagnostic biomarker change p-value t-value Phosphatidylethanolamine 1.329 0.00142 3.231 (C18:0, C22:6) Lysophosphatidylethanolamine 0.897 0.05226 1.951 (C18:0) Sphingomyelin (35:1) 1.096 0.08245 1.744

TABLE-US-00004 TABLE 4 List of identified biomarkers in plasma for pancreatic cancer relative to diabetic subjects (from chronic pancreatitis, non-pancreatic controls, diabetes group) ANOVA result of pancreatic cancer relative to diabetic subjects (from chronic pancreatitis, non-pancreatic controls, diabetes group) Estimated fold Diagnostic biomarker change p-value t-value Lysophosphatidylethanolamine 0.663 0.0000012 4.952 (C18:2) Proline 0.789 0.0000021 4.836 Sphingomyelin (35:1) 1.240 0.00005 4.117 Sphingomyelin (d18:2, C17:0) 1.209 0.00010 3.947 Phosphatidylethanolamine 1.390 0.00032 3.634 (C18:0, C22:6) Sphingomyelin (d17:1, C16:0) 1.212 0.00054 3.494 Histidine 0.912 0.00178 3.151 Sphingomyelin (41:2) 1.151 0.00215 3.093 Tryptophan 0.872 0.00219 3.088 Lysophosphatidylethanolamine 0.858 0.00426 2.879 (C18:0) Ceramide (d18:1, C24:0) 0.861 0.00797 2.670 Ceramide (d18:2, C24:0) 0.822 0.00797 2.670

TABLE-US-00005 TABLE 5 List of identified biomarkers in plasma for resectable pancreatic cancer relative to chronic pancreatitis ANOVA result of resectable pancreatic cancer relative to chronic pancreatitis Estimated fold Diagnostic biomarker change p-value t-value Sphingomyelin (35:1) 1.271 0.00140 3.242 Ceramide (d18:1, C24:0) 0.799 0.00930 2.628 Phosphatidylethanolamine 1.363 0.01124 2.560 (C18:0, C22:6) Ceramide (d18:2, C24:0) 0.772 0.02307 2.291 Lysophosphatidylethanolamine 0.874 0.08510 1.731 (C18:0) Tryptophan 0.927 0.27129 1.103

TABLE-US-00006 TABLE 6 List of identified biomarkers in plasma for resectable pancreatic cancer relative to non-pancreatic control ANOVA result of resectable pancreatic cancer relative to non-pancreatic controls Estimated fold Diagnostic biomarker change p-value t-value Proline 0.805 0.00096 3.356 Ceramide (d18:2, C24:0) 0.731 0.00163 3.197 Ceramide (d18:1, C24:0) 0.805 0.00394 2.919 Phosphatidylethanolamine 1.348 0.00496 2.843 (C18:0, C22:6) Tryptophan 0.856 0.00932 2.627 Histidine 0.919 0.03148 2.167 Lysophosphatidylethanolamine 0.881 0.06323 1.868 (C18:0) Sphingomyelin (35:1) 1.118 0.08464 1.733 Sphingomyelin (d18:2, C17:0) 1.094 0.14099 1.478 Sphingomyelin (d17:1, C16:0) 1.073 0.30992 1.018 Sphingomyelin (41:2) 1.019 0.75048 0.318

TABLE-US-00007 TABLE 7 List of identified biomarkers in plasma for resectable pancreatic cancer relative to diabetic subjects (from chronic pancreatitis, non-pancreatic controls, diabetes group) ANOVA result of resectable pancreatic cancer relative to diabetic subjects (from chronic pancreatitis, non- pancreatic control, diabetes group) Estimated fold Diagnostic biomarker change p-value t-value Lysophosphatidylethanolamine 0.644 0.00001 4.541 (C18:2) Proline 0.797 0.00020 3.769 Sphingomyelin (35:1) 1.267 0.00025 3.712 Sphingomyelin (d18:2, C17:0) 1.229 0.00052 3.508 Phosphatidylethanolamine 1.436 0.00094 3.343 (C18:0, C22:6) Tryptophan 0.851 0.00238 3.066 Sphingomyelin (d17:1, C16:0) 1.219 0.00372 2.925 Ceramide (d18:1, C24:0) 0.822 0.00375 2.922 Ceramide (d18:2, C24:0) 0.793 0.00809 2.667 Sphingomyelin (41:2) 1.154 0.01058 2.573 Lysophosphatidylethanolamine 0.862 0.01971 2.345 (C18:0) Histidine 0.929 0.03442 2.125

[0216] Classification using the Elastic Net algorithm (Zou and Hastie (2005) Regularization and variable selection via the elastic net, Journal of the Royal Statistical Society, Series B: 67, 301-320) as implemented in the R (version 3.0.1) package glmnet (version 1.9-8) was calculated to obtain a logistic regression model on log 10 transformed data including CA 19-9. The L1 and the L2 penalties were given equal weight. The log-transformed biomarker data including CA19-9 were also centered and scaled to unit variance before the analysis. This logistic regression models allows the calculation of predicted probabilities for each of the patients having pancreatic cancer.

[0217] A10-fold cross-validation was used to obtain an unbiased estimate of the area under the curve (AUC) on the remaining fold. The 95% confidence intervals for the AUC were calculated using the binormal model of the receiver operating characteristic (ROC) curve as described in Zhou, Obuchowski and McClish [Statistical Methods in Diagnostic Medicine (2011), 2nd Edition, by Zhou, Obuchowski and McClish]. The assumption of the binormality of the logit-transformed prediction scores was visually checked with a QQ-Plot. Afterwards the final model coefficients were determined by retraining the classifier on the entire data.

EXAMPLE 5: BIOMARKER PANEL FOR DIAGNOSIS OF PANCREATIC CANCER

[0218] The diagnostic biomarkers of the biomarker panels allowing for diagnosis of pancreatic cancer versus chronic pancreatitis, pancreatic cancer versus non-pancreatic control, and pancreatic cancer versus (chronic pancreatitis plus non pancreatic control), were manually selected and optimized according to their discriminating performance both multivariate and univariate and the feasibility of their concomitant analysis in a single analytical approach. These pre-defined panels were then tested for their discrimination performance using Elastic Net algorithm combined with ROC curve analysis.

[0219] The biomarker panels that were identified for diagnosis of pancreatic cancer consist of a most preferred core panel that comprises in addition to CA19-9 at least one small molecule biomarker from each of the metabolite classes amino acids, ceramides, and sphingomyelins as shown in Table 8A. Frequently, the biomarker panels comprised in addition to CA19-9 at least one small molecule biomarker from each of the metabolite classes amino acids, ceramides, sphingomyelins, and ethanolamine lipids as shown in Table 8B.

TABLE-US-00008 TABLE 8A Core panel definition for diagnosis of pancreatic cancer Panel CA19-9 Amino acid Ceramide Sphingomyelin Core panel CA19-9 x x x

TABLE-US-00009 TABLE 8B Extended core panel definition for diagnosis of pancreatic cancer Amino Cera- Ethanolamine Panel CA19-9 acid mide Sphingomyelin lipid Extended CA19-9 x x x x core panel

[0220] The core panel structure shown in Tables 8A or 8B can be composed of the following biomarkers: [0221] amino acids: proline, and/or tryptophan, and/or histidine [0222] ceramides: ceramide (d18:1,C24:0) and/or ceramide (d18:2,C24:0) [0223] sphingomyelins: Sphingomyelin (35:1), and/or sphingomyelin (d17:1,C16:0), and/or sphingomyelin (d18:2,C17:0), and/or (Sphingomyelin (41:2)) [0224] ethanolamine lipids: Phosphatidylethanolamine (C18:0,C22:6), and/or lysophosphatidylethanolamine (C18:2) and/or lysophosphatidylethanolamine (C18:0)

[0225] Respective biomarker panels of the invention are shown in Table 9, below:

TABLE-US-00010 TABLE 9 Panel composition for diagnosis of pancreatic cancer Panel Number Panel Composition 1 CA19-9, Ceramide (d18:1, C24:0), Proline, Sphingomyelin (35:1) 2 CA19-9, Ceramide (d18:1, C24:0), Phosphatidylethanolamine (C18:0, C22:6), Proline, Sphingomyelin (35:1) 3 CA19-9, Ceramide (d18:1, C24:0), Lysophosphatidylethanolamine (C18:2), Proline, Sphingomyelin (35:1) 4 CA19-9, Ceramide (d18:1, C24:0), Lysophosphatidylethanolamine (C18:0), Proline, Sphingomyelin (35:1) 5 CA19-9, Ceramide (d18:1, C24:0), Lysophosphatidylethanolamine (C18:2), Proline, Sphingomyelin (35:1) 6 CA19-9, Ceramide (d18:1, C24:0), Lysophosphatidylethanolamine (C18:2), Proline, Sphingomyelin (35:1), Sphingomyelin (d18:2, C17:0) 7 CA19-9, Ceramide (d18:1, C24:0), Proline, Sphingomyelin (35:1), Sphingomyelin (d18:2, C17:0), Tryptophan 8 CA19-9, Ceramide (d18:1, C24:0), Lysophosphatidylethanolamine (C18:2), Proline, Sphingomyelin (35:1), Sphingomyelin (d18:2, C17:0), Tryptophan 9 CA19-9, Ceramide (d18:1, C24:0), Lysophosphatidylethanolamine (C18:2), Phosphatidylethanolamine (C18:0, C22:6), Proline, Sphingomyelin (35:1), Tryptophan 10 CA19-9, Ceramide (d18:1, C24:0), Lysophosphatidylethanolamine (C18:2), Phosphatidylethanolamine (C18:0, C22:6), Proline, Sphingomyelin (35:1), Sphingomyelin (d18:2, C17:0), Tryptophan 11 CA19-9, Ceramide (d18:1, C24:0), Lysophosphatidylethanolamine (C18:0), Lysophosphatidylethanolamine (C18:2), Phosphatidylethanolamine (C18:0, C22:6), Proline, Sphingomyelin (35:1), Sphingomyelin (d18:2, C17:0), Tryptophan 12 CA19-9, Ceramide (d18:2, C24:0), Proline, Sphingomyelin (35:1) 13 CA19-9, Ceramide (d18:2, C24:0), Phosphatidylethanolamine (C18:0, C22:6), Proline, Sphingomyelin (35:1) 14 CA19-9, Ceramide (d18:2, C24:0), Lysophosphatidylethanolamine (C18:0), Proline, Sphingomyelin (35:1) 15 CA19-9, Ceramide (d18:2, C24:0), Lysophosphatidylethanolamine (C18:2), Proline, Sphingomyelin (35:1) 16 CA19-9, Ceramide (d18:1, C24:0), Proline, Sphingomyelin (d17:1, C16:0) 17 CA19-9, Ceramide (d18:1, C24:0), Proline, Sphingomyelin (41:2) 18 CA19-9, Ceramide (d18:1, C24:0), Proline, Sphingomyelin (d18:2, C17:0) 19 CA19-9, Ceramide (d18:2, C24:0), Proline, Sphingomyelin (d17:1, C16:0) 20 CA19-9, Ceramide (d18:2, C24:0), Proline, Sphingomyelin (41:2) 21 CA19-9, Ceramide (d18:2, C24:0), Proline, Sphingomyelin (d18:2, C17:0) 22 CA19-9, Ceramide (d18:1, C24:0), Histidine, Sphingomyelin (35:1) 23 CA19-9, Ceramide (d18:1, C24:0), Histidine, Sphingomyelin (d17:1, C16:0) 24 CA19-9, Ceramide (d18:1, C24:0), Histidine, Sphingomyelin (41:2) 25 CA19-9, Ceramide (d18:1, C24:0), Histidine, Sphingomyelin (d18:2, C17:0) 26 CA19-9, Ceramide (d18:2, C24:0), Histidine, Sphingomyelin (35:1) 27 CA19-9, Ceramide (d18:2, C24:0), Histidine, Sphingomyelin (d17:1, C16:0) 28 CA19-9, Ceramide (d18:2, C24:0), Histidine, Sphingomyelin (41:2) 29 CA19-9, Ceramide (d18:2, C24:0), Histidine, Sphingomyelin (d18:2, C17:0) 30 CA19-9, Ceramide (d18:1, C24:0), Sphingomyelin (35:1), Tryptophan 31 CA19-9, Ceramide (d18:1, C24:0), Sphingomyelin (41:2), Tryptophan 32 CA19-9, Ceramide (d18:1, C24:0), Sphingomyelin (d18:2, C17:0), Tryptophan 33 CA19-9, Ceramide (d18:1, C24:0), Sphingomyelin (d17:1, C16:0), Tryptophan 34 CA19-9, Ceramide (d18:2, C24:0), Sphingomyelin (35:1), Tryptophan 35 CA19-9, Ceramide (d18:2, C24:0), Sphingomyelin (d17:1, C16:0), Tryptophan 36 CA19-9, Ceramide (d18:2, C24:0), Sphingomyelin (41:2), Tryptophan 37 CA19-9, Ceramide (d18:2, C24:0), Sphingomyelin (d18:2, C17:0), Tryptophan 38 CA19-9, Ceramide (d18:1, C24:0), Lysophosphatidylethanolamine (C18:2), Proline, Sphingomyelin (d17:1, C16:0) 39 CA19-9, Ceramide (d18:1, C24:0), Lysophosphatidylethanolamine (C18:2), Proline, Sphingomyelin (41:2) 40 CA19-9, Ceramide (d18:1, C24:0), Lysophosphatidylethanolamine (C18:2), Proline, Sphingomyelin (d18:2, C17:0) 41 CA19-9, Ceramide (d18:1, C24:0), Lysophosphatidylethanolamine (C18:0), Proline, Sphingomyelin (d17:1, C16:0) 42 CA19-9, Ceramide (d18:1, C24:0), Lysophosphatidylethanolamine (C18:0), Proline, Sphingomyelin (41:2) 43 CA19-9, Ceramide (d18:1, C24:0), Phosphatidylethanolamine (C18:0, C22:6), Proline, Sphingomyelin (d17:1, C16:0) 44 CA19-9, Ceramide (d18:1, C24:0), Phosphatidylethanolamine (C18:0, C22:6), Proline, Sphingomyelin (41:2) 45 CA19-9, Ceramide (d18:1, C24:0), Lysophosphatidylethanolamine (C18:0), Proline, Sphingomyelin (d18:2, C17:0) 46 CA19-9, Ceramide (d18:1, C24:0), Phosphatidylethanolamine (C18:0, C22:6), Proline, Sphingomyelin (d18:2, C17:0) 47 CA19-9, Ceramide (d18:2, C24:0), Phosphatidylethanolamine (C18:0, C22:6), Proline, Sphingomyelin (d17:1, C16:0) 48 CA19-9, Ceramide (d18:2, C24:0), Phosphatidylethanolamine (C18:0, C22:6), Proline, Sphingomyelin (41:2) 49 CA19-9, Ceramide (d18:2, C24:0), Phosphatidylethanolamine (C18:0, C22:6), Proline, Sphingomyelin (d18:2, C17:0) 50 CA19-9, Ceramide (d18:2, C24:0), Lysophosphatidylethanolamine (C18:0), Proline, Sphingomyelin (d17:1, C16:0) 51 CA19-9, Ceramide (d18:2, C24:0), Lysophosphatidylethanolamine (C18:0), Proline, Sphingomyelin (41:2) 52 CA19-9, Ceramide (d18:2, C24:0), Lysophosphatidylethanolamine (C18:0), Proline, Sphingomyelin (d18:2, C17:0) 53 CA19-9, Ceramide (d18:2, C24:0), Lysophosphatidylethanolamine (C18:2), Proline, Sphingomyelin (d17:1, C16:0) 54 CA19-9, Ceramide (d18:2, C24:0), Lysophosphatidylethanolamine (C18:2), Proline, Sphingomyelin (41:2) 55 CA19-9, Ceramide (d18:2, C24:0), Lysophosphatidylethanolamine (C18:2), Proline, Sphingomyelin (d18:2, C17:0) 56 CA19-9, Ceramide (d18:1, C24:0), Histidine, Lysophosphatidylethanolamine (C18:0), Sphingomyelin (35:1) 57 CA19-9, Ceramide (d18:1, C24:0), Histidine, Lysophosphatidylethanolamine (C18:2), Sphingomyelin (35:1) 58 CA19-9, Ceramide (d18:1, C24:0), Histidine, Phosphatidylethanolamine (C18:0, C22:6), Sphingomyelin (35:1) 59 CA19-9, Ceramide (d18:1, C24:0), Histidine, Lysophosphatidylethanolamine (C18:0), Sphingomyelin (d17:1, C16:0) 60 CA19-9, Ceramide (d18:1, C24:0), Histidine, Lysophosphatidylethanolamine (C18:0), Sphingomyelin (41:2) 61 CA19-9, Ceramide (d18:1, C24:0), Histidine, Lysophosphatidylethanolamine (C18:2), Sphingomyelin (d17:1, C16:0) 62 CA19-9, Ceramide (d18:1, C24:0), Histidine, Lysophosphatidylethanolamine (C18:2), Sphingomyelin (41:2) 63 CA19-9, Ceramide (d18:1, C24:0), Histidine, Lysophosphatidylethanolamine (C18:0), Sphingomyelin (d18:2, C17:0) 64 CA19-9, Ceramide (d18:1, C24:0), Histidine, Lysophosphatidylethanolamine (C18:2), Sphingomyelin (d18:2, C17:0) 65 CA19-9, Ceramide (d18:1, C24:0), Histidine, Phosphatidylethanolamine (C18:0, C22:6), Sphingomyelin (d17:1, C16:0) 66 CA19-9, Ceramide (d18:1, C24:0), Histidine, Phosphatidylethanolamine (C18:0, C22:6), Sphingomyelin (41:2) 67 CA19-9, Ceramide (d18:1, C24:0), Histidine, Phosphatidylethanolamine (C18:0, C22:6), Sphingomyelin (d18:2, C17:0) 68 CA19-9, Ceramide (d18:2, C24:0), Histidine, Lysophosphatidylethanolamine (C18:0), Sphingomyelin (35:1) 69 CA19-9, Ceramide (d18:2, C24:0), Histidine, Lysophosphatidylethanolamine (C18:2), Sphingomyelin (35:1) 70 CA19-9, Ceramide (d18:2, C24:0), Histidine, Phosphatidylethanolamine (C18:0, C22:6), Sphingomyelin (35:1) 71 CA19-9, Ceramide (d18:2, C24:0), Histidine, Phosphatidylethanolamine (C18:0, C22:6), Sphingomyelin (d18:2, C17:0) 72 CA19-9, Ceramide (d18:2, C24:0), Histidine, Lysophosphatidylethanolamine (C18:0), Sphingomyelin (d17:1, C16:0) 73 CA19-9, Ceramide (d18:2, C24:0), Histidine, Lysophosphatidylethanolamine (C18:0), Sphingomyelin (41:2) 74 CA19-9, Ceramide (d18:2, C24:0), Histidine, Lysophosphatidylethanolamine (C18:0), Sphingomyelin (d18:2, C17:0) 75 CA19-9, Ceramide (d18:2, C24:0), Histidine, Lysophosphatidylethanolamine (C18:2), Sphingomyelin (d17:1, C16:0) 76 CA19-9, Ceramide (d18:2, C24:0), Histidine, Lysophosphatidylethanolamine (C18:2), Sphingomyelin (41:2) 77 CA19-9, Ceramide (d18:2, C24:0), Histidine, Lysophosphatidylethanolamine (C18:2), Sphingomyelin (d18:2, C17:0) 78 CA19-9, Ceramide (d18:2, C24:0), Histidine, Phosphatidylethanolamine (C18:0, C22:6), Sphingomyelin (d17:1, C16:0) 79 CA19-9, Ceramide (d18:2, C24:0), Histidine, Phosphatidylethanolamine (C18:0, C22:6), Sphingomyelin (41:2) 80 CA19-9, Ceramide (d18:1, C24:0), Lysophosphatidylethanolamine (C18:0), Sphingomyelin (35:1), Tryptophan 81 CA19-9, Ceramide (d18:1, C24:0), Lysophosphatidylethanolamine (C18:2), Sphingomyelin (35:1), Tryptophan 82 CA19-9, Ceramide (d18:1, C24:0), Phosphatidylethanolamine (C18:0, C22:6), Sphingomyelin (35:1), Tryptophan 83 CA19-9, Ceramide (d18:1, C24:0), Lysophosphatidylethanolamine (C18:0), Sphingomyelin (41:2), Tryptophan 84 CA19-9, Ceramide (d18:1, C24:0), Lysophosphatidylethanolamine (C18:0), Sphingomyelin (d18:2, C17:0), Tryptophan 85 CA19-9, Ceramide (d18:1, C24:0), Lysophosphatidylethanolamine (C18:2), Sphingomyelin (d17:1, C16:0), Tryptophan 86 CA19-9, Ceramide (d18:1, C24:0), Lysophosphatidylethanolamine (C18:2), Sphingomyelin (41:2), Tryptophan 87 CA19-9, Ceramide (d18:1, C24:0), Lysophosphatidylethanolamine (C18:2), Sphingomyelin (d18:2, C17:0), Tryptophan 88 CA19-9, Ceramide (d18:1, C24:0), Phosphatidylethanolamine (C18:0, C22:6), Sphingomyelin (d17:1, C16:0), Tryptophan 89 CA19-9, Ceramide (d18:1, C24:0), Phosphatidylethanolamine (C18:0, C22:6), Sphingomyelin (41:2), Tryptophan 90 CA19-9, Ceramide (d18:1, C24:0), Phosphatidylethanolamine (C18:0, C22:6), Sphingomyelin (d18:2, C17:0), Tryptophan 91 CA19-9, Ceramide (d18:1, C24:0), Lysophosphatidylethanolamine (C18:0), Sphingomyelin (d17:1, C16:0), Tryptophan 92 CA19-9, Ceramide (d18:2, C24:0), Phosphatidylethanolamine (C18:0, C22:6), Sphingomyelin (35:1), Tryptophan 93 CA19-9, Ceramide (d18:2, C24:0), Lysophosphatidylethanolamine (C18:0), Sphingomyelin (35:1), Tryptophan 94 CA19-9, Ceramide (d18:2, C24:0), Lysophosphatidylethanolamine (C18:2), Sphingomyelin (35:1), Tryptophan 95 CA19-9, Ceramide (d18:2, C24:0), Phosphatidylethanolamine (C18:0, C22:6), Sphingomyelin (d17:1, C16:0), Tryptophan 96 CA19-9, Ceramide (d18:2, C24:0), Phosphatidylethanolamine (C18:0, C22:6), Sphingomyelin (41:2), Tryptophan 97 CA19-9, Ceramide (d18:2, C24:0), Phosphatidylethanolamine (C18:0, C22:6), Sphingomyelin (d18:2, C17:0), Tryptophan 98 CA19-9, Ceramide (d18:2, C24:0), Lysophosphatidylethanolamine (C18:0), Sphingomyelin (d17:1, C16:0), Tryptophan 99 CA19-9, Ceramide (d18:2, C24:0), Lysophosphatidylethanolamine (C18:0), Sphingomyelin (41:2), Tryptophan 100 CA19-9, Ceramide (d18:2, C24:0), Lysophosphatidylethanolamine (C18:0), Sphingomyelin (d18:2, C17:0), Tryptophan 101 CA19-9, Ceramide (d18:2, C24:0), Lysophosphatidylethanolamine (C18:2), Sphingomyelin (d17:1, C16:0), Tryptophan 102 CA19-9, Ceramide (d18:2, C24:0), Lysophosphatidylethanolamine (C18:2), Sphingomyelin (41:2), Tryptophan 103 CA19-9, Ceramide (d18:2, C24:0), Lysophosphatidylethanolamine (C18:2), Sphingomyelin (d18:2, C17:0), Tryptophan 104 CA19-9, Ceramide (d18:1, C24:0), Ceramide (d18:2, C24:0), Histidine, Lysophosphatidylethanolamine (C18:0), Lysophosphatidylethanolamine (C18:2), Phosphatidylethanolamine (C18:0, C22:6), Proline, Sphingomyelin (d17:1, C16:0), Sphingomyelin (35:1), Sphingomyelin (41:2), Sphingomyelin (d18:2, C17:0), Tryptophan

[0226] All panels were analyzed for their discrimination performance of pancreatic cancer versus chronic pancreatitis; pancreatic cancer versus non-pancreatic control; pancreatic cancer versus (chronic pancreatitis plus non-pancreatic control) as described in Example 4. The panels shown in Table 9 performed as listed in Table 10, below. The diagnostic performance is in all cases increased compared to CA19-9 alone: CA19-9 alone resulted in AUC of discrimination performance of pancreatic cancer versus chronic pancreatitis; pancreatic cancer versus non-pancreatic control; pancreatic cancer versus (chronic pancreatitis plus non-pancreatic control) of 0.83, 0.87, and 0.85, respectively. In the resectable pancreatic cancer subgroup, CA19-9 alone resulted in AUC of discrimination performance of pancreatic cancer versus chronic pancreatitis; pancreatic cancer versus non-pancreatic control; pancreatic cancer versus (chronic pancreatitis plus non-pancreatic control) of 0.80, 0.86, and 0.84, respectively. In the low CA19-9 (<37 U/ml) subgroup, CA19-9 alone resulted in AUC of discrimination performance of pancreatic cancer versus chronic pancreatitis; pancreatic cancer versus non-pancreatic control; pancreatic cancer versus (chronic pancreatitis plus non-pancreatic control) of 0.53, 0.56, and 0.54, respectively.

TABLE-US-00011 TABLE 10 Diagnostic performance of the panels shown in Table 9 for detection of pancreatic cancer AUC of AUC of comparison AUC of comparison of comparison of of pancreatic pancreatic cancer pancreatic cancer cancer relative relative to (chronic Panel relative to chronic to non-pancreatic pancreatitis and non- Number pancreatitis controls pancreatic controls) 1 0.913 0.897 0.899 2 0.929 0.897 0.901 3 0.916 0.893 0.897 4 0.912 0.897 0.898 5 0.916 0.893 0.897 6 0.913 0.891 0.894 7 0.916 0.894 0.896 8 0.914 0.887 0.894 9 0.928 0.889 0.899 10 0.925 0.888 0.896 11 0.93 0.888 0.896 12 0.908 0.897 0.899 13 0.92 0.895 0.899 14 0.908 0.897 0.898 15 0.911 0.893 0.897 16 0.903 0.895 0.891 17 0.912 0.889 0.892 18 0.908 0.893 0.892 19 0.896 0.896 0.892 20 0.907 0.892 0.896 21 0.901 0.895 0.893 22 0.905 0.886 0.887 23 0.895 0.882 0.879 24 0.907 0.881 0.886 25 0.902 0.883 0.881 26 0.898 0.885 0.886 27 0.885 0.881 0.878 28 0.901 0.883 0.888 29 0.891 0.881 0.881 30 0.918 0.889 0.894 31 0.919 0.882 0.892 32 0.908 0.885 0.887 33 0.903 0.884 0.885 34 0.911 0.884 0.891 35 0.896 0.881 0.882 36 0.912 0.882 0.892 37 0.899 0.881 0.885 38 0.906 0.891 0.89 39 0.915 0.886 0.891 40 0.908 0.888 0.89 41 0.902 0.895 0.89 42 0.909 0.89 0.891 43 0.916 0.896 0.892 44 0.926 0.894 0.894 45 0.906 0.893 0.892 46 0.921 0.893 0.893 47 0.906 0.894 0.89 48 0.917 0.893 0.895 49 0.91 0.892 0.891 50 0.898 0.895 0.892 51 0.906 0.892 0.895 52 0.901 0.893 0.892 53 0.9 0.892 0.891 54 0.909 0.887 0.893 55 0.9 0.888 0.891 56 0.908 0.885 0.885 57 0.913 0.884 0.89 58 0.923 0.887 0.893 59 0.897 0.881 0.877 60 0.907 0.88 0.884 61 0.901 0.883 0.884 62 0.912 0.879 0.888 63 0.901 0.881 0.878 64 0.903 0.88 0.883 65 0.909 0.883 0.883 66 0.921 0.883 0.89 67 0.914 0.882 0.884 68 0.903 0.884 0.886 69 0.907 0.882 0.89 70 0.914 0.883 0.888 71 0.902 0.88 0.88 72 0.893 0.88 0.878 73 0.903 0.881 0.886 74 0.895 0.88 0.879 75 0.892 0.881 0.883 76 0.904 0.88 0.889 77 0.894 0.879 0.882 78 0.896 0.881 0.879 79 0.911 0.883 0.889 80 0.916 0.888 0.891 81 0.917 0.885 0.894 82 0.929 0.889 0.896 83 0.917 0.882 0.889 84 0.906 0.884 0.884 85 0.904 0.883 0.887 86 0.918 0.879 0.89 87 0.905 0.881 0.885 88 0.912 0.886 0.885 89 0.928 0.885 0.892 90 0.917 0.885 0.887 91 0.902 0.884 0.882 92 0.918 0.884 0.891 93 0.911 0.883 0.888 94 0.912 0.882 0.893 95 0.901 0.881 0.881 96 0.916 0.883 0.891 97 0.905 0.881 0.884 98 0.897 0.88 0.879 99 0.911 0.88 0.889 100 0.9 0.88 0.882 101 0.896 0.881 0.886 102 0.911 0.877 0.891 103 0.899 0.878 0.886 104 0.922 0.896 0.891

[0227] A classifier of pancreatic cancer diagnosis was obtained by training the elastic net algorithm on the predefined panels as described by Zou and Hastie ((2005) Regularization and variable selection via the elastic net, Journal of the Royal Statistical Society, Series B, 67, 301-320) using the pancreatic cancer group as positive class and the chronic pancreatitis and/or the non-pancreatic controls as negative class, respectively. In order to reduce overfitting effects, tenfold cross-validation was done which is well known to a person skilled in the art. As a result, for each of the classifiers weightings and scalings are obtained that are optimized for the classes they were trained for.

[0228] Those classifiers are subsequently tested by the same and further classification tasks, those being pancreatic cancer relative to chronic pancreatitis, pancreatic cancer relative to non-pancreatic controls, pancreatic cancer relative to (chronic pancreatitis and non-pancreatic controls), pancreatic cancer relative to all non-cancer subjects (chronic pancreatitis, non-pancreatic controls, diabetes group, non-diabetes group, and pancreatic cancer relative to diabetic subjects (from chronic pancreatitis, non-pancreatic controls, diabetes group). Each of those comparisons were applied on either the entire data set, or the resectable pancreatic cancer group, or the low CA19-9 group.

[0229] After training the panels on the differentiation of pancreatic cancer versus chronic pancreatitis, and pancreatic cancer versus non-pancreatic controls, and pancreatic cancer versus (chronic pancreatitis plus non-pancreatic controls), the resulting biomarkers were analyzed for their performance in the training groups, diabetic subgroups and all non-cancer subjects including the 104 extra diabetic and non-diabetic samples (see Example 1). In addition, these biomarker panel were evaluated on the samples from patients with resectable pancreatic cancer and to samples from patients with low (<37 U/ml) CA19-9 values in order to analyze their performance on less progressive cancer states and for potential lewis a/b negative subjects that will give false-negative CA19-9 levels. The AUC subgroup performance of the panels from Table 9 is shown in Table 11, below:

TABLE-US-00012 TABLE 11 Subgroup performance of the diagnostic biomarker panels shown in Table 9 including diabetes, resectable pancreatic cancer and low CA19-9. Panel Number Training of panel on A B C D E F 1 PDCA vs (CP + all 0.902 0.895 0.899 0.906 0.908 non-pancreatic ctrl) 1 PDCA vs (CP + low CA19-9 0.756 0.678 0.714 0.700 0.659 non-pancreatic ctrl) 1 PDCA vs (CP + resectable 0.890 0.883 0.887 0.896 0.898 non-pancreatic ctrl) 1 PDCA vs CP all 0.913 0.896 0.904 0.913 0.915 1 PDCA vs CP low CA19-9 0.829 0.734 0.777 0.771 0.736 1 PDCA vs CP resectable 0.909 0.892 0.900 0.911 0.914 1 PDCA vs non- all 0.897 0.897 0.897 0.905 0.910 pancreatic ctrl 1 PDCA vs non- low CA19-9 0.749 0.675 0.708 0.687 0.643 pancreatic ctrl 1 PDCA vs non- resectable 0.886 0.886 0.886 0.897 0.904 pancreatic ctrl 2 PDCA vs (CP + all 0.911 0.890 0.901 0.909 0.910 non-pancreatic ctrl) 2 PDCA vs (CP + low CA19-9 0.792 0.694 0.738 0.727 0.690 non-pancreatic ctrl) 2 PDCA vs (CP + resectable 0.896 0.872 0.884 0.893 0.894 non-pancreatic ctrl) 2 PDCA vs CP all 0.929 0.892 0.911 0.919 0.921 2 PDCA vs CP low CA19-9 0.879 0.771 0.820 0.816 0.789 2 PDCA vs CP resectable 0.920 0.878 0.899 0.908 0.910 2 PDCA vs non- all 0.906 0.897 0.902 0.909 0.914 pancreatic ctrl 2 PDCA vs non- low CA19-9 0.777 0.683 0.724 0.703 0.661 pancreatic ctrl 2 PDCA vs non- resectable 0.896 0.885 0.891 0.900 0.907 pancreatic ctrl 3 PDCA vs (CP + all 0.902 0.892 0.897 0.904 0.902 non-pancreatic ctrl) 3 PDCA vs (CP + low CA19-9 0.757 0.676 0.713 0.695 0.642 non-pancreatic ctrl) 3 PDCA vs (CP + resectable 0.891 0.880 0.885 0.893 0.891 non-pancreatic ctrl) 3 PDCA vs CP all 0.916 0.895 0.905 0.913 0.913 3 PDCA vs CP low CA19-9 0.837 0.744 0.787 0.779 0.737 3 PDCA vs CP resectable 0.911 0.888 0.899 0.908 0.909 3 PDCA vs non- all 0.896 0.893 0.894 0.903 0.907 pancreatic ctrl 3 PDCA vs non- low CA19-9 0.747 0.670 0.704 0.683 0.635 pancreatic ctrl 3 PDCA vs non- resectable 0.886 0.882 0.884 0.895 0.901 pancreatic ctrl 4 PDCA vs (CP + all 0.902 0.894 0.898 0.904 0.904 non-pancreatic ctrl) 4 PDCA vs (CP + low CA19-9 0.756 0.676 0.713 0.694 0.646 non-pancreatic ctrl) 4 PDCA vs (CP + resectable 0.890 0.881 0.886 0.893 0.893 non-pancreatic ctrl) 4 PDCA vs CP all 0.912 0.893 0.902 0.900 0.890 4 PDCA vs CP low CA19-9 0.827 0.725 0.772 0.735 0.664 4 PDCA vs CP resectable 0.909 0.888 0.898 0.896 0.886 4 PDCA vs non- all 0.896 0.897 0.896 0.905 0.910 pancreatic ctrl 4 PDCA vs non- low CA19-9 0.746 0.673 0.705 0.685 0.641 pancreatic ctrl 4 PDCA vs non- resectable 0.886 0.887 0.887 0.897 0.905 pancreatic ctrl 5 PDCA vs (CP + all 0.902 0.892 0.897 0.904 0.902 non-pancreatic ctrl) 5 PDCA vs (CP + low CA19-9 0.757 0.676 0.713 0.695 0.642 non-pancreatic ctrl) 5 PDCA vs (CP + resectable 0.891 0.880 0.885 0.893 0.891 non-pancreatic ctrl) 5 PDCA vs CP all 0.916 0.895 0.905 0.913 0.913 5 PDCA vs CP low CA19-9 0.837 0.744 0.787 0.779 0.737 5 PDCA vs CP resectable 0.911 0.888 0.899 0.908 0.909 5 PDCA vs non- all 0.896 0.893 0.894 0.903 0.907 pancreatic ctrl 5 PDCA vs non- low CA19-9 0.747 0.670 0.704 0.683 0.635 pancreatic ctrl 5 PDCA vs non- resectable 0.886 0.882 0.884 0.895 0.901 pancreatic ctrl 6 PDCA vs (CP + all 0.900 0.888 0.894 0.901 0.901 non-pancreatic ctrl) 6 PDCA vs (CP + low CA19-9 0.757 0.669 0.709 0.693 0.643 non-pancreatic ctrl) 6 PDCA vs (CP + resectable 0.888 0.873 0.881 0.889 0.889 non-pancreatic ctrl) 6 PDCA vs CP all 0.913 0.890 0.901 0.910 0.912 6 PDCA vs CP low CA19-9 0.836 0.741 0.784 0.780 0.745 6 PDCA vs CP resectable 0.906 0.881 0.893 0.903 0.906 6 PDCA vs non- all 0.894 0.891 0.893 0.901 0.905 pancreatic ctrl 6 PDCA vs non- low CA19-9 0.744 0.666 0.700 0.680 0.631 pancreatic ctrl 6 PDCA vs non- resectable 0.883 0.879 0.881 0.892 0.898 pancreatic ctrl 7 PDCA vs (CP + all 0.901 0.890 0.896 0.906 0.912 non-pancreatic ctrl) 7 PDCA vs (CP + low CA19-9 0.758 0.676 0.713 0.709 0.681 non-pancreatic ctrl) 7 PDCA vs (CP + resectable 0.885 0.872 0.879 0.891 0.898 non-pancreatic ctrl) 7 PDCA vs CP all 0.916 0.890 0.903 0.916 0.925 7 PDCA vs CP low CA19-9 0.843 0.748 0.791 0.801 0.790 7 PDCA vs CP resectable 0.907 0.878 0.893 0.907 0.917 7 PDCA vs non- all 0.891 0.894 0.893 0.904 0.913 pancreatic ctrl 7 PDCA vs non- low CA19-9 0.738 0.670 0.700 0.690 0.659 pancreatic ctrl 7 PDCA vs non- resectable 0.873 0.876 0.875 0.888 0.900 pancreatic ctrl 8 PDCA vs (CP + all 0.900 0.887 0.894 0.902 0.905 non-pancreatic ctrl) 8 PDCA vs (CP + low CA19-9 0.756 0.670 0.710 0.699 0.656 non-pancreatic ctrl) 8 PDCA vs (CP + resectable 0.885 0.870 0.878 0.888 0.890 non-pancreatic ctrl) 8 PDCA vs CP all 0.914 0.888 0.901 0.912 0.918 8 PDCA vs CP low CA19-9 0.840 0.744 0.788 0.793 0.771 8 PDCA vs CP resectable 0.906 0.877 0.891 0.904 0.911 8 PDCA vs non- all 0.888 0.887 0.888 0.899 0.908 pancreatic ctrl 8 PDCA vs non- low CA19-9 0.728 0.658 0.689 0.676 0.640 pancreatic ctrl 8 PDCA vs non- resectable 0.870 0.868 0.869 0.883 0.893 pancreatic ctrl 9 PDCA vs (CP + all 0.910 0.887 0.899 0.907 0.909 non-pancreatic ctrl) 9 PDCA vs (CP + low CA19-9 0.782 0.685 0.729 0.719 0.681 non-pancreatic ctrl) 9 PDCA vs (CP + resectable 0.893 0.866 0.880 0.889 0.890 non-pancreatic ctrl) 9 PDCA vs CP all 0.928 0.889 0.908 0.919 0.922 9 PDCA vs CP low CA19-9 0.873 0.765 0.814 0.815 0.791 9 PDCA vs CP resectable 0.918 0.875 0.896 0.908 0.911 9 PDCA vs non- all 0.898 0.889 0.894 0.904 0.912 pancreatic ctrl 9 PDCA vs non- low CA19-9 0.752 0.665 0.703 0.688 0.653 pancreatic ctrl 9 PDCA vs non- resectable 0.881 0.871 0.877 0.889 0.899 pancreatic ctrl 10 PDCA vs (CP + all 0.908 0.884 0.896 0.905 0.907 non-pancreatic ctrl) 10 PDCA vs (CP + low CA19-9 0.781 0.682 0.727 0.718 0.681 non-pancreatic ctrl) 10 PDCA vs (CP + resectable 0.890 0.862 0.876 0.886 0.888 non-pancreatic ctrl) 10 PDCA vs CP all 0.925 0.886 0.905 0.917 0.922 10 PDCA vs CP low CA19-9 0.872 0.764 0.813 0.817 0.797 10 PDCA vs CP resectable 0.914 0.870 0.892 0.904 0.909 10 PDCA vs non- all 0.897 0.888 0.893 0.903 0.911 pancreatic ctrl 10 PDCA vs non- low CA19-9 0.751 0.662 0.701 0.687 0.653 pancreatic ctrl 10 PDCA vs non- resectable 0.879 0.869 0.874 0.887 0.897 pancreatic ctrl 11 PDCA vs (CP + all 0.908 0.883 0.896 0.903 0.904 non-pancreatic ctrl) 11 PDCA vs (CP + low CA19-9 0.782 0.681 0.727 0.714 0.673 non-pancreatic ctrl) 11 PDCA vs (CP + resectable 0.890 0.861 0.876 0.885 0.885 non-pancreatic ctrl) 11 PDCA vs CP all 0.930 0.881 0.906 0.899 0.883 11 PDCA vs CP low CA19-9 0.892 0.768 0.824 0.786 0.718 11 PDCA vs CP resectable 0.921 0.866 0.894 0.886 0.868 11 PDCA vs non- all 0.897 0.888 0.893 0.903 0.911 pancreatic ctrl 11 PDCA vs non- low CA19-9 0.751 0.662 0.701 0.687 0.653 pancreatic ctrl 11 PDCA vs non- resectable 0.879 0.869 0.874 0.887 0.897 pancreatic ctrl 12 PDCA vs (CP + all 0.900 0.897 0.899 0.905 0.907 non-pancreatic ctrl) 12 PDCA vs (CP + low CA19-9 0.761 0.693 0.724 0.707 0.664 non-pancreatic ctrl) 12 PDCA vs (CP + resectable 0.884 0.881 0.883 0.890 0.893 non-pancreatic ctrl) 12 PDCA vs CP all 0.908 0.891 0.899 0.906 0.907 12 PDCA vs CP low CA19-9 0.821 0.734 0.774 0.762 0.725 12 PDCA vs CP resectable 0.902 0.883 0.892 0.901 0.902 12 PDCA vs non- all 0.892 0.897 0.895 0.904 0.911 pancreatic ctrl 12 PDCA vs non- low CA19-9 0.744 0.686 0.712 0.694 0.654 pancreatic ctrl 12 PDCA vs non- resectable 0.878 0.885 0.882 0.894 0.903 pancreatic ctrl 13 PDCA vs (CP + all 0.907 0.891 0.899 0.906 0.907 non-pancreatic ctrl) 13 PDCA vs (CP + low CA19-9 0.787 0.701 0.740 0.724 0.687 non-pancreatic ctrl) 13 PDCA vs (CP + resectable 0.888 0.869 0.879 0.886 0.887 non-pancreatic ctrl) 13 PDCA vs CP all 0.920 0.886 0.903 0.910 0.911 13 PDCA vs CP low CA19-9 0.868 0.769 0.814 0.804 0.776 13 PDCA vs CP resectable 0.908 0.870 0.889 0.896 0.897 13 PDCA vs non- all 0.898 0.895 0.897 0.906 0.913 pancreatic ctrl 13 PDCA vs non- low CA19-9 0.766 0.689 0.722 0.704 0.665 pancreatic ctrl 13 PDCA vs non- resectable 0.886 0.882 0.884 0.895 0.905 pancreatic ctrl 14 PDCA vs (CP + all 0.900 0.895 0.898 0.902 0.900 non-pancreatic ctrl) 14 PDCA vs (CP + low CA19-9 0.758 0.687 0.720 0.695 0.642 non-pancreatic ctrl) 14 PDCA vs (CP + resectable 0.883 0.878 0.881 0.886 0.884 non-pancreatic ctrl) 14 PDCA vs CP all 0.908 0.887 0.897 0.891 0.876 14 PDCA vs CP low CA19-9 0.820 0.723 0.768 0.719 0.638 14 PDCA vs CP resectable 0.903 0.881 0.892 0.885 0.869 14 PDCA vs non- all 0.891 0.897 0.894 0.904 0.911 pancreatic ctrl 14 PDCA vs non- low CA19-9 0.741 0.684 0.709 0.691 0.651 pancreatic ctrl 14 PDCA vs non- resectable 0.877 0.885 0.881 0.893 0.903 pancreatic ctrl 15 PDCA vs (CP + all 0.901 0.894 0.897 0.903 0.901 non-pancreatic ctrl) 15 PDCA vs (CP + low CA19-9 0.756 0.683 0.717 0.695 0.641 non-pancreatic ctrl) 15 PDCA vs (CP + resectable 0.886 0.877 0.882 0.888 0.886 non-pancreatic ctrl) 15 PDCA vs CP all 0.911 0.890 0.900 0.906 0.904 15 PDCA vs CP low CA19-9 0.822 0.736 0.776 0.761 0.714 15 PDCA vs CP resectable 0.903 0.879 0.891 0.898 0.896 15 PDCA vs non- all 0.890 0.893 0.891 0.901 0.908 pancreatic ctrl 15 PDCA vs non- low CA19-9 0.737 0.677 0.704 0.686 0.642 pancreatic ctrl 15 PDCA vs non- resectable 0.878 0.881 0.880 0.892 0.901 pancreatic ctrl 16 PDCA vs (CP + all 0.891 0.890 0.891 0.897 0.901 non-pancreatic ctrl) 16 PDCA vs (CP + low CA19-9 0.731 0.658 0.691 0.675 0.637 non-pancreatic ctrl) 16 PDCA vs (CP + resectable 0.877 0.875 0.876 0.884 0.889 non-pancreatic ctrl) 16 PDCA vs CP all 0.903 0.892 0.897 0.905 0.909 16 PDCA vs CP low CA19-9 0.810 0.714 0.758 0.749 0.718 16 PDCA vs CP resectable 0.893 0.881 0.887 0.896 0.901 16 PDCA vs non- all 0.886 0.895 0.891 0.899 0.906 pancreatic ctrl 16 PDCA vs non- low CA19-9 0.720 0.659 0.686 0.664 0.624 pancreatic ctrl 16 PDCA vs non- resectable 0.870 0.881 0.876 0.887 0.897 pancreatic ctrl 17 PDCA vs (CP + all 0.892 0.892 0.892 0.901 0.910 non-pancreatic ctrl) 17 PDCA vs (CP + low CA19-9 0.719 0.643 0.677 0.667 0.640 non-pancreatic ctrl) 17 PDCA vs (CP + resectable 0.878 0.878 0.878 0.890 0.900 non-pancreatic ctrl) 17 PDCA vs CP all 0.912 0.893 0.902 0.915 0.927 17 PDCA vs CP low CA19-9 0.809 0.692 0.746 0.750 0.741 17 PDCA vs CP resectable 0.901 0.878 0.889 0.904 0.919 17 PDCA vs non- all 0.865 0.889 0.877 0.886 0.897 pancreatic ctrl 17 PDCA vs non- low CA19-9 0.659 0.633 0.644 0.622 0.585 pancreatic ctrl 17 PDCA vs non- resectable 0.844 0.873 0.859 0.871 0.885 pancreatic ctrl 18 PDCA vs (CP + all 0.894 0.891 0.892 0.901 0.909 non-pancreatic ctrl) 18 PDCA vs (CP + low CA19-9 0.738 0.660 0.696 0.688 0.660 non-pancreatic ctrl) 18 PDCA vs (CP + resectable 0.878 0.874 0.876 0.887 0.896 non-pancreatic ctrl) 18 PDCA vs CP all 0.908 0.893 0.901 0.912 0.920 18 PDCA vs CP low CA19-9 0.819 0.721 0.766 0.768 0.751 18 PDCA vs CP resectable 0.897 0.880 0.889 0.902 0.912 18 PDCA vs non- all 0.884 0.893 0.889 0.898 0.907 pancreatic ctrl 18 PDCA vs non- low CA19-9 0.714 0.655 0.681 0.663 0.627 pancreatic ctrl 18 PDCA vs non- resectable 0.868 0.879 0.874 0.886 0.897 pancreatic ctrl 19 PDCA vs (CP + all 0.890 0.894 0.892 0.898 0.902 non-pancreatic ctrl) 19 PDCA vs (CP + low CA19-9 0.736 0.676 0.704 0.683 0.645 non-pancreatic ctrl) 19 PDCA vs (CP + resectable 0.872 0.876 0.874 0.880 0.885 non-pancreatic ctrl) 19 PDCA vs CP all 0.896 0.887 0.891 0.897 0.898 19 PDCA vs CP low CA19-9 0.797 0.714 0.752 0.737 0.704 19 PDCA vs CP resectable 0.883 0.873 0.878 0.885 0.887 19 PDCA vs non- all 0.882 0.896 0.889 0.899 0.909 pancreatic ctrl 19 PDCA vs non- low CA19-9 0.716 0.673 0.692 0.674 0.640 pancreatic ctrl 19 PDCA vs non- resectable 0.863 0.881 0.872 0.885 0.898 pancreatic ctrl 20 PDCA vs (CP + all 0.895 0.897 0.896 0.906 0.915 non-pancreatic ctrl) 20 PDCA vs (CP + low CA19-9 0.739 0.670 0.702 0.691 0.666 non-pancreatic ctrl) 20 PDCA vs (CP + resectable 0.876 0.879 0.877 0.889 0.900 non-pancreatic ctrl) 20 PDCA vs CP all 0.907 0.890 0.898 0.910 0.920 20 PDCA vs CP low CA19-9 0.803 0.701 0.748 0.748 0.737 20 PDCA vs CP resectable 0.891 0.870 0.880 0.894 0.907 20 PDCA vs non- all 0.867 0.892 0.880 0.892 0.905 pancreatic ctrl 20 PDCA vs non- low CA19-9 0.674 0.656 0.664 0.649 0.618 pancreatic ctrl 20 PDCA vs non- resectable 0.845 0.876 0.861 0.876 0.893 pancreatic ctrl 21 PDCA vs (CP + all 0.892 0.893 0.893 0.901 0.910 non-pancreatic ctrl) 21 PDCA vs (CP + low CA19-9 0.744 0.677 0.708 0.697 0.670 non-pancreatic ctrl) 21 PDCA vs (CP + resectable 0.871 0.873 0.872 0.882 0.892 non-pancreatic ctrl) 21 PDCA vs CP all 0.901 0.889 0.895 0.904 0.912 21 PDCA vs CP low CA19-9 0.806 0.722 0.760 0.757 0.738 21 PDCA vs CP resectable 0.886 0.872 0.879 0.890 0.899 21 PDCA vs non- all 0.882 0.895 0.889 0.900 0.911 pancreatic ctrl 21 PDCA vs non- low CA19-9 0.719 0.673 0.693 0.679 0.649 pancreatic ctrl 21 PDCA vs non- resectable 0.864 0.879 0.872 0.886 0.900 pancreatic ctrl 22 PDCA vs (CP + all 0.892 0.881 0.887 0.892 0.884 non-pancreatic ctrl) 22 PDCA vs (CP + low CA19-9 0.719 0.642 0.677 0.659 0.604 non-pancreatic ctrl) 22 PDCA vs (CP + resectable 0.886 0.873 0.880 0.887 0.878 non-pancreatic ctrl) 22 PDCA vs CP all 0.905 0.882 0.894 0.900 0.894 22 PDCA vs CP low CA19-9 0.809 0.704 0.752 0.742 0.687 22 PDCA vs CP resectable 0.906 0.882 0.893 0.902 0.896 22 PDCA vs non- all 0.881 0.886 0.884 0.888 0.880 pancreatic ctrl 22 PDCA vs non- low CA19-9 0.694 0.636 0.662 0.632 0.561 pancreatic ctrl 22 PDCA vs non- resectable 0.873 0.879 0.877 0.883 0.875 pancreatic ctrl 23 PDCA vs (CP + all 0.880 0.877 0.879 0.883 0.876 non-pancreatic ctrl) 23 PDCA vs (CP + low CA19-9 0.688 0.623 0.652 0.631 0.577 non-pancreatic ctrl) 23 PDCA vs (CP + resectable 0.871 0.866 0.869 0.874 0.866 non-pancreatic ctrl) 23 PDCA vs CP all 0.895 0.877 0.886 0.891 0.884 23 PDCA vs CP low CA19-9 0.789 0.685 0.733 0.718 0.664 23 PDCA vs CP resectable 0.887 0.868 0.877 0.884 0.877 23 PDCA vs non- all 0.867 0.882 0.875 0.879 0.873 pancreatic ctrl 23 PDCA vs non- low CA19-9 0.657 0.617 0.635 0.604 0.536 pancreatic ctrl 23 PDCA vs non- resectable 0.852 0.870 0.862 0.868 0.861 pancreatic ctrl 24 PDCA vs (CP + all 0.889 0.883 0.886 0.893 0.892 non-pancreatic ctrl) 24 PDCA vs (CP + low CA19-9 0.704 0.626 0.661 0.648 0.605 non-pancreatic ctrl) 24 PDCA vs (CP + resectable 0.879 0.872 0.876 0.885 0.883 non-pancreatic ctrl) 24 PDCA vs CP all 0.907 0.882 0.895 0.905 0.907 24 PDCA vs CP low CA19-9 0.803 0.679 0.736 0.736 0.704 24 PDCA vs CP resectable 0.899 0.870 0.884 0.896 0.900 24 PDCA vs non- all 0.862 0.881 0.872 0.877 0.873 pancreatic ctrl 24 PDCA vs non- low CA19-9 0.644 0.614 0.627 0.599 0.535 pancreatic ctrl 24 PDCA vs non- resectable 0.846 0.869 0.858 0.865 0.861 pancreatic ctrl 25 PDCA vs (CP + all 0.885 0.878 0.881 0.888 0.887 non-pancreatic ctrl) 25 PDCA vs (CP + low CA19-9 0.705 0.629 0.663 0.651 0.609 non-pancreatic ctrl) 25 PDCA vs (CP + resectable 0.874 0.866 0.870 0.879 0.878 non-pancreatic ctrl) 25 PDCA vs CP all 0.902 0.882 0.892 0.901 0.902 25 PDCA vs CP low CA19-9 0.806 0.701 0.749 0.749 0.714 25 PDCA vs CP resectable 0.895 0.873 0.884 0.895 0.897 25 PDCA vs non- all 0.872 0.883 0.878 0.883 0.878 pancreatic ctrl 25 PDCA vs non- low CA19-9 0.676 0.625 0.648 0.619 0.554 pancreatic ctrl 25 PDCA vs non- resectable 0.859 0.872 0.866 0.873 0.868 pancreatic ctrl 26 PDCA vs (CP + all 0.889 0.882 0.886 0.890 0.883 non-pancreatic ctrl) 26 PDCA vs (CP + low CA19-9 0.715 0.647 0.678 0.656 0.600 non-pancreatic ctrl) 26 PDCA vs (CP + resectable 0.878 0.870 0.874 0.879 0.871 non-pancreatic ctrl) 26 PDCA vs CP all 0.898 0.875 0.887 0.891 0.884 26 PDCA vs CP low CA19-9 0.796 0.702 0.745 0.730 0.675 26 PDCA vs CP resectable 0.894 0.869 0.882 0.888 0.880 26 PDCA vs non- all 0.874 0.885 0.879 0.885 0.878 pancreatic ctrl 26 PDCA vs non- low CA19-9 0.682 0.637 0.657 0.627 0.557 pancreatic ctrl 26 PDCA vs non- resectable 0.861 0.874 0.868 0.875 0.869 pancreatic ctrl 27 PDCA vs (CP + all 0.878 0.878 0.878 0.881 0.874 non-pancreatic ctrl) 27 PDCA vs (CP + low CA19-9 0.683 0.629 0.653 0.627 0.572 non-pancreatic ctrl) 27 PDCA vs (CP + resectable 0.863 0.863 0.863 0.867 0.859 non-pancreatic ctrl) 27 PDCA vs CP all 0.885 0.870 0.878 0.881 0.874 27 PDCA vs CP low CA19-9 0.773 0.683 0.724 0.704 0.649 27 PDCA vs CP resectable 0.874 0.857 0.865 0.869 0.861 27 PDCA vs non- all 0.859 0.881 0.870 0.876 0.872 pancreatic ctrl 27 PDCA vs non- low CA19-9 0.642 0.619 0.629 0.599 0.534 pancreatic ctrl 27 PDCA vs non- resectable 0.840 0.867 0.854 0.861 0.859 pancreatic ctrl 28 PDCA vs (CP + all 0.889 0.886 0.888 0.895 0.894 non-pancreatic ctrl) 28 PDCA vs (CP + low CA19-9 0.711 0.641 0.673 0.657 0.614 non-pancreatic ctrl) 28 PDCA vs (CP + resectable 0.873 0.870 0.872 0.880 0.880 non-pancreatic ctrl) 28 PDCA vs CP all 0.901 0.879 0.890 0.899 0.901 28 PDCA vs CP low CA19-9 0.796 0.687 0.737 0.735 0.702 28 PDCA vs CP resectable 0.886 0.860 0.873 0.884 0.887 28 PDCA vs non- all 0.861 0.883 0.872 0.879 0.878 pancreatic ctrl 28 PDCA vs non- low CA19-9 0.646 0.627 0.635 0.610 0.548 pancreatic ctrl 28 PDCA vs non- resectable 0.841 0.868 0.855 0.865 0.863 pancreatic ctrl 29 PDCA vs (CP + all 0.882 0.879 0.881 0.887 0.887 non-pancreatic ctrl) 29 PDCA vs (CP + low CA19-9 0.704 0.636 0.667 0.652 0.609 non-pancreatic ctrl) 29 PDCA vs (CP + resectable 0.866 0.862 0.864 0.872 0.871 non-pancreatic ctrl) 29 PDCA vs CP all 0.891 0.875 0.883 0.891 0.892 29 PDCA vs CP low CA19-9 0.787 0.696 0.738 0.733 0.697 29 PDCA vs CP resectable 0.880 0.861 0.871 0.880 0.882 29 PDCA vs non- all 0.865 0.881 0.874 0.880 0.877 pancreatic ctrl 29 PDCA vs non- low CA19-9 0.664 0.629 0.644 0.618 0.554 pancreatic ctrl 29 PDCA vs non- resectable 0.849 0.868 0.859 0.867 0.865 pancreatic ctrl 30 PDCA vs (CP + all 0.901 0.886 0.894 0.904 0.907 non-pancreatic ctrl) 30 PDCA vs (CP + low CA19-9 0.744 0.664 0.700 0.697 0.664 non-pancreatic ctrl) 30 PDCA vs (CP + resectable 0.891 0.874 0.883 0.895 0.899 non-pancreatic ctrl) 30 PDCA vs CP all 0.918 0.886 0.902 0.915 0.919 30 PDCA vs CP low CA19-9 0.838 0.733 0.781 0.790 0.767 30 PDCA vs CP resectable 0.914 0.880 0.897 0.912 0.916 30 PDCA vs non- all 0.884 0.889 0.886 0.898 0.905 pancreatic ctrl 30 PDCA vs non- low CA19-9 0.700 0.646 0.670 0.662 0.624 pancreatic ctrl 30 PDCA vs non- resectable 0.872 0.878 0.875 0.890 0.898 pancreatic ctrl 31 PDCA vs (CP + all 0.897 0.886 0.892 0.905 0.917 non-pancreatic ctrl) 31 PDCA vs (CP + low CA19-9 0.729 0.644 0.681 0.687 0.675 non-pancreatic ctrl) 31 PDCA vs (CP + resectable 0.883 0.870 0.877 0.893 0.907 non-pancreatic ctrl) 31 PDCA vs CP all 0.919 0.885 0.902 0.920 0.934 31 PDCA vs CP low CA19-9 0.832 0.703 0.762 0.784 0.789 31 PDCA vs CP resectable 0.908 0.870 0.889 0.908 0.925 31 PDCA vs non- all 0.862 0.882 0.872 0.887 0.901 pancreatic ctrl 31 PDCA vs non- low CA19-9 0.645 0.620 0.631 0.629 0.606 pancreatic ctrl 31 PDCA vs non- resectable 0.841 0.866 0.854 0.872 0.889 pancreatic ctrl 32 PDCA vs (CP + all 0.891 0.881 0.887 0.898 0.908 non-pancreatic ctrl) 32 PDCA vs (CP + low CA19-9 0.728 0.649 0.684 0.686 0.667 non-pancreatic ctrl) 32 PDCA vs (CP + resectable 0.877 0.865 0.871 0.885 0.897 non-pancreatic ctrl) 32 PDCA vs CP all 0.908 0.883 0.895 0.909 0.919 32 PDCA vs CP low CA19-9 0.821 0.716 0.764 0.778 0.768 32 PDCA vs CP resectable 0.898 0.869 0.884 0.899 0.910 32 PDCA vs non- all 0.873 0.885 0.879 0.892 0.903 pancreatic ctrl 32 PDCA vs non- low CA19-9 0.678 0.634 0.653 0.649 0.622 pancreatic ctrl 32 PDCA vs non- resectable 0.855 0.869 0.862 0.879 0.892 pancreatic ctrl 33 PDCA vs (CP + all 0.889 0.881 0.885 0.895 0.900 non-pancreatic ctrl) 33 PDCA vs (CP + low CA19-9 0.713 0.644 0.674 0.669 0.641 non-pancreatic ctrl) 33 PDCA vs (CP + resectable 0.876 0.868 0.872 0.884 0.890 non-pancreatic ctrl) 33 PDCA vs CP all 0.903 0.879 0.891 0.903 0.907 33 PDCA vs CP low CA19-9 0.807 0.701 0.749 0.754 0.731 33 PDCA vs CP resectable 0.894 0.867 0.881 0.894 0.899 33 PDCA vs non- all 0.869 0.884 0.877 0.890 0.900 pancreatic ctrl 33 PDCA vs non- low CA19-9 0.663 0.627 0.643 0.636 0.606 pancreatic ctrl 33 PDCA vs non- resectable 0.851 0.869 0.860 0.876 0.889 pancreatic ctrl 34 PDCA vs (CP + all 0.897 0.885 0.891 0.900 0.903 non-pancreatic ctrl) 34 PDCA vs (CP + low CA19-9 0.738 0.666 0.698 0.690 0.655 non-pancreatic ctrl) 34 PDCA vs (CP + resectable 0.884 0.870 0.877 0.887 0.891 non-pancreatic ctrl) 34 PDCA vs CP all 0.911 0.879 0.895 0.907 0.910 34 PDCA vs CP low CA19-9 0.826 0.726 0.771 0.777 0.752 34 PDCA vs CP resectable 0.905 0.869 0.887 0.901 0.904 34 PDCA vs non- all 0.875 0.884 0.880 0.892 0.899 pancreatic ctrl 34 PDCA vs non- low CA19-9 0.683 0.640 0.659 0.650 0.613 pancreatic ctrl 34 PDCA vs non- resectable 0.861 0.872 0.867 0.882 0.891 pancreatic ctrl 35 PDCA vs (CP + all 0.884 0.881 0.882 0.891 0.896 non-pancreatic ctrl) 35 PDCA vs (CP + low CA19-9 0.702 0.644 0.670 0.660 0.630 non-pancreatic ctrl) 35 PDCA vs (CP + resectable 0.867 0.864 0.866 0.876 0.882 non-pancreatic ctrl) 35 PDCA vs CP all 0.896 0.875 0.885 0.895 0.899 35 PDCA vs CP low CA19-9 0.794 0.699 0.742 0.742 0.718 35 PDCA vs CP resectable 0.883 0.859 0.871 0.883 0.887 35 PDCA vs non- all 0.861 0.881 0.871 0.884 0.895 pancreatic ctrl 35 PDCA vs non- low CA19-9 0.646 0.624 0.633 0.626 0.595 pancreatic ctrl 35 PDCA vs non- resectable 0.840 0.865 0.853 0.869 0.883 pancreatic ctrl 36 PDCA vs (CP + all 0.897 0.888 0.892 0.905 0.917 non-pancreatic ctrl) 36 PDCA vs (CP + low CA19-9 0.736 0.655 0.691 0.694 0.681 non-pancreatic ctrl) 36 PDCA vs (CP + resectable 0.878 0.868 0.873 0.888 0.903 non-pancreatic ctrl) 36 PDCA vs CP all 0.912 0.881 0.897 0.913 0.926 36 PDCA vs CP low CA19-9 0.821 0.702 0.755 0.775 0.777 36 PDCA vs CP resectable 0.896 0.860 0.878 0.897 0.912 36 PDCA vs non- all 0.859 0.882 0.871 0.887 0.901 pancreatic ctrl 36 PDCA vs non- low CA19-9 0.644 0.627 0.634 0.633 0.608 pancreatic ctrl 36 PDCA vs non- resectable 0.837 0.864 0.850 0.870 0.888 pancreatic ctrl 37 PDCA vs (CP + all 0.888 0.881 0.885 0.895 0.905 non-pancreatic ctrl) 37 PDCA vs (CP + low CA19-9 0.720 0.652 0.682 0.680 0.660 non-pancreatic ctrl) 37 PDCA vs (CP + resectable 0.869 0.862 0.866 0.879 0.889 non-pancreatic ctrl) 37 PDCA vs CP all 0.899 0.877 0.888 0.901 0.911 37 PDCA vs CP low CA19-9 0.806 0.711 0.754 0.764 0.754 37 PDCA vs CP resectable 0.885 0.860 0.873 0.887 0.898 37 PDCA vs non- all 0.867 0.881 0.874 0.888 0.899 pancreatic ctrl 37 PDCA vs non- low CA19-9 0.668 0.632 0.647 0.642 0.614 pancreatic ctrl 37 PDCA vs non- resectable 0.847 0.865 0.856 0.873 0.887 pancreatic ctrl 38 PDCA vs (CP + all 0.892 0.888 0.890 0.896 0.895 non-pancreatic ctrl) 38 PDCA vs (CP + low CA19-9 0.736 0.660 0.694 0.673 0.622 non-pancreatic ctrl) 38 PDCA vs (CP + resectable 0.879 0.874 0.877 0.883 0.883 non-pancreatic ctrl) 38 PDCA vs CP all 0.906 0.888 0.897 0.903 0.904 38 PDCA vs CP low CA19-9 0.821 0.723 0.768 0.755 0.714 38 PDCA vs CP resectable 0.898 0.878 0.888 0.896 0.897 38 PDCA vs non- all 0.886 0.891 0.889 0.897 0.904 pancreatic ctrl 38 PDCA vs non- low CA19-9 0.721 0.657 0.685 0.663 0.617 pancreatic ctrl 38 PDCA vs non- resectable 0.871 0.877 0.875 0.886 0.895 pancreatic ctrl 39 PDCA vs (CP + all 0.893 0.889 0.891 0.900 0.905 non-pancreatic ctrl) 39 PDCA vs (CP + low CA19-9 0.720 0.641 0.677 0.662 0.622 non-pancreatic ctrl) 39 PDCA vs (CP + resectable 0.879 0.874 0.877 0.887 0.893 non-pancreatic ctrl) 39 PDCA vs CP all 0.915 0.888 0.901 0.914 0.923 39 PDCA vs CP low CA19-9 0.820 0.701 0.755 0.758 0.738 39 PDCA vs CP resectable 0.902 0.872 0.887 0.901 0.913 39 PDCA vs non- all 0.865 0.886 0.876 0.885 0.895 pancreatic ctrl 39 PDCA vs non- low CA19-9 0.660 0.631 0.644 0.620 0.579 pancreatic ctrl 39 PDCA vs non- resectable 0.844 0.869 0.857 0.869 0.883 pancreatic ctrl 40 PDCA vs (CP + all 0.892 0.887 0.890 0.898 0.904 non-pancreatic ctrl) 40 PDCA vs (CP + low CA19-9 0.736 0.654 0.691 0.679 0.641 non-pancreatic ctrl) 40 PDCA vs (CP + resectable 0.876 0.869 0.873 0.882 0.889 non-pancreatic ctrl) 40 PDCA vs CP all 0.908 0.890 0.899 0.910 0.917 40 PDCA vs CP low CA19-9 0.821 0.726 0.770 0.770 0.746 40 PDCA vs CP resectable 0.898 0.878 0.888 0.900 0.908 40 PDCA vs non- all 0.882 0.888 0.886 0.895 0.904 pancreatic ctrl 40 PDCA vs non- low CA19-9 0.711 0.651 0.677 0.658 0.617 pancreatic ctrl 40 PDCA vs non- resectable 0.867 0.873 0.870 0.882 0.894 pancreatic ctrl 41 PDCA vs (CP + all 0.891 0.889 0.890 0.895 0.896 non-pancreatic ctrl) 41 PDCA vs (CP + low CA19-9 0.727 0.653 0.687 0.665 0.620 non-pancreatic ctrl) 41 PDCA vs (CP + resectable 0.875 0.873 0.874 0.880 0.882 non-pancreatic ctrl) 41 PDCA vs CP all 0.902 0.889 0.895 0.893 0.885 41 PDCA vs CP low CA19-9 0.807 0.704 0.752 0.712 0.648 41 PDCA vs CP resectable 0.894 0.879 0.886 0.884 0.876 41 PDCA vs non- all 0.885 0.895 0.890 0.899 0.906 pancreatic ctrl 41 PDCA vs non- low CA19-9 0.718 0.659 0.685 0.663 0.623 pancreatic ctrl 41 PDCA vs non- resectable 0.870 0.882 0.876 0.887 0.898 pancreatic ctrl 42 PDCA vs (CP + all 0.890 0.891 0.891 0.900 0.908 non-pancreatic ctrl) 42 PDCA vs (CP + low CA19-9 0.714 0.640 0.674 0.662 0.632 non-pancreatic ctrl) 42 PDCA vs (CP + resectable 0.876 0.877 0.876 0.887 0.897 non-pancreatic ctrl) 42 PDCA vs CP all 0.909 0.887 0.898 0.904 0.909 42 PDCA vs CP low CA19-9 0.800 0.678 0.734 0.717 0.684 42 PDCA vs CP resectable 0.899 0.873 0.886 0.892 0.899 42 PDCA vs non- all 0.867 0.890 0.878 0.888 0.898 pancreatic ctrl 42 PDCA vs non- low CA19-9 0.662 0.636 0.648 0.627 0.590 pancreatic ctrl 42 PDCA vs non- resectable 0.847 0.875 0.861 0.873 0.887 pancreatic ctrl 43 PDCA vs (CP + all 0.899 0.886 0.892 0.900 0.903 non-pancreatic ctrl) 43 PDCA vs (CP + low CA19-9 0.767 0.677 0.717 0.704 0.669 non-pancreatic ctrl) 43 PDCA vs (CP + resectable 0.881 0.865 0.873 0.882 0.885 non-pancreatic ctrl) 43 PDCA vs CP all 0.916 0.888 0.902 0.910 0.914 43 PDCA vs CP low CA19-9 0.856 0.750 0.798 0.792 0.768 43 PDCA vs CP resectable 0.903 0.870 0.887 0.896 0.900 43 PDCA vs non- all 0.895 0.896 0.896 0.904 0.911 pancreatic ctrl 43 PDCA vs non- low CA19-9 0.750 0.671 0.705 0.684 0.646 pancreatic ctrl 43 PDCA vs non- resectable 0.882 0.882 0.882 0.892 0.903 pancreatic ctrl 44 PDCA vs (CP + all 0.901 0.886 0.894 0.904 0.911 non-pancreatic ctrl) 44 PDCA vs (CP + low CA19-9 0.759 0.662 0.706 0.699 0.672 non-pancreatic ctrl) 44 PDCA vs (CP + resectable 0.882 0.864 0.873 0.885 0.893 non-pancreatic ctrl) 44 PDCA vs CP all 0.926 0.890 0.908 0.921 0.931 44 PDCA vs CP low CA19-9 0.860 0.738 0.793 0.798 0.789 44 PDCA vs CP resectable 0.912 0.870 0.891 0.905 0.916 44 PDCA vs non- all 0.883 0.894 0.889 0.897 0.907 pancreatic ctrl 44 PDCA vs non- low CA19-9 0.712 0.658 0.682 0.660 0.625 pancreatic ctrl 44 PDCA vs non- resectable 0.865 0.878 0.872 0.883 0.895 pancreatic ctrl 45 PDCA vs (CP + all 0.893 0.890 0.892 0.899 0.906 non-pancreatic ctrl) 45 PDCA vs (CP + low CA19-9 0.735 0.657 0.693 0.681 0.648 non-pancreatic ctrl) 45 PDCA vs (CP + resectable 0.877 0.873 0.875 0.884 0.892 non-pancreatic ctrl) 45 PDCA vs CP all 0.906 0.889 0.897 0.900 0.901 45 PDCA vs CP low CA19-9 0.813 0.710 0.757 0.735 0.692 45 PDCA vs CP resectable 0.896 0.877 0.886 0.889 0.890 45 PDCA vs non- all 0.884 0.893 0.889 0.898 0.907 pancreatic ctrl 45 PDCA vs non- low CA19-9 0.714 0.655 0.681 0.663 0.627 pancreatic ctrl 45 PDCA vs non- resectable 0.868 0.879 0.874 0.886 0.897 pancreatic ctrl 46 PDCA vs (CP + all 0.901 0.885 0.893 0.902 0.910 non-pancreatic ctrl) 46 PDCA vs (CP + low CA19-9 0.768 0.674 0.717 0.710 0.684 non-pancreatic ctrl) 46 PDCA vs (CP + resectable 0.881 0.862 0.872 0.882 0.890 non-pancreatic ctrl) 46 PDCA vs CP all 0.921 0.891 0.906 0.917 0.926 46 PDCA vs CP low CA19-9 0.862 0.757 0.805 0.807 0.794 46 PDCA vs CP resectable 0.907 0.872 0.890 0.902 0.911 46 PDCA vs non- all 0.893 0.893 0.893 0.902 0.909 pancreatic ctrl 46 PDCA vs non- low CA19-9 0.744 0.665 0.700 0.681 0.643 pancreatic ctrl 46 PDCA vs non- resectable 0.878 0.877 0.878 0.889 0.899 pancreatic ctrl 47 PDCA vs (CP + all 0.894 0.886 0.890 0.896 0.899 non-pancreatic ctrl) 47 PDCA vs (CP + low CA19-9 0.761 0.685 0.719 0.702 0.666 non-pancreatic ctrl) 47 PDCA vs (CP + resectable 0.873 0.863 0.868 0.875 0.878 non-pancreatic ctrl) 47 PDCA vs CP all 0.906 0.882 0.894 0.900 0.902 47 PDCA vs CP low CA19-9 0.845 0.751 0.794 0.781 0.756 47 PDCA vs CP resectable 0.891 0.863 0.877 0.884 0.887 47 PDCA vs non- all 0.889 0.894 0.892 0.901 0.911 pancreatic ctrl 47 PDCA vs non- low CA19-9 0.742 0.678 0.706 0.687 0.654 pancreatic ctrl 47 PDCA vs non- resectable 0.873 0.879 0.876 0.888 0.901 pancreatic ctrl 48 PDCA vs (CP + all 0.899 0.890 0.895 0.904 0.912 non-pancreatic ctrl) 48 PDCA vs (CP + low CA19-9 0.766 0.682 0.720 0.710 0.686 non-pancreatic ctrl) 48 PDCA vs (CP + resectable 0.877 0.865 0.871 0.882 0.891 non-pancreatic ctrl) 48 PDCA vs CP all 0.917 0.886 0.901 0.913 0.923 48 PDCA vs CP low CA19-9 0.852 0.744 0.793 0.794 0.785 48 PDCA vs CP resectable 0.898 0.861 0.880 0.892 0.903 48 PDCA vs non- all 0.879 0.893 0.887 0.897 0.910 pancreatic ctrl 48 PDCA vs non- low CA19-9 0.715 0.670 0.690 0.673 0.644 pancreatic ctrl 48 PDCA vs non- resectable 0.861 0.878 0.869 0.883 0.899 pancreatic ctrl 49 PDCA vs (CP + all 0.896 0.886 0.891 0.900 0.908 non-pancreatic ctrl) 49 PDCA vs (CP + low CA19-9 0.766 0.684 0.721 0.711 0.685 non-pancreatic ctrl) 49 PDCA vs (CP + resectable 0.872 0.861 0.867 0.876 0.885 non-pancreatic ctrl) 49 PDCA vs CP all 0.910 0.885 0.898 0.907 0.915 49 PDCA vs CP low CA19-9 0.848 0.756 0.798 0.795 0.780 49 PDCA vs CP resectable 0.891 0.863 0.877 0.887 0.897 49 PDCA vs non- all 0.888 0.892 0.890 0.901 0.910 pancreatic ctrl 49 PDCA vs non- low CA19-9 0.741 0.675 0.704 0.688 0.655 pancreatic ctrl 49 PDCA vs non- resectable 0.871 0.876 0.874 0.887 0.899 pancreatic ctrl 50 PDCA vs (CP + all 0.890 0.893 0.892 0.895 0.896 non-pancreatic ctrl) 50 PDCA vs (CP + low CA19-9 0.736 0.673 0.702 0.674 0.625 non-pancreatic ctrl) 50 PDCA vs (CP + resectable 0.871 0.873 0.872 0.876 0.877 non-pancreatic ctrl) 50 PDCA vs CP all 0.898 0.885 0.891 0.883 0.871 50 PDCA vs CP low CA19-9 0.799 0.705 0.748 0.694 0.619 50 PDCA vs CP resectable 0.887 0.873 0.880 0.871 0.858 50 PDCA vs non- all 0.880 0.895 0.888 0.898 0.907 pancreatic ctrl 50 PDCA vs non- low CA19-9 0.712 0.670 0.688 0.671 0.635 pancreatic ctrl 50 PDCA vs non- resectable 0.862 0.880 0.871 0.884 0.897 pancreatic ctrl 51 PDCA vs (CP + all 0.893 0.896 0.895 0.903 0.911 non-pancreatic ctrl) 51 PDCA vs (CP + low CA19-9 0.731 0.664 0.694 0.680 0.649 non-pancreatic ctrl) 51 PDCA vs (CP + resectable 0.873 0.877 0.875 0.885 0.894 non-pancreatic ctrl) 51 PDCA vs CP all 0.906 0.887 0.896 0.898 0.900 51 PDCA vs CP low CA19-9 0.797 0.687 0.738 0.710 0.669 51 PDCA vs CP resectable 0.891 0.868 0.879 0.882 0.883 51 PDCA vs non- all 0.867 0.892 0.880 0.892 0.905 pancreatic ctrl 51 PDCA vs non- low CA19-9 0.672 0.655 0.662 0.647 0.616 pancreatic ctrl 51 PDCA vs non- resectable 0.845 0.876 0.861 0.876 0.893 pancreatic ctrl 52 PDCA vs (CP + all 0.891 0.892 0.892 0.898 0.904 non-pancreatic ctrl) 52 PDCA vs (CP + low CA19-9 0.740 0.671 0.702 0.684 0.648 non-pancreatic ctrl) 52 PDCA vs (CP + resectable 0.871 0.871 0.871 0.879 0.885 non-pancreatic ctrl) 52 PDCA vs CP all 0.901 0.887 0.894 0.892 0.890 52 PDCA vs CP low CA19-9 0.804 0.712 0.754 0.720 0.668 52 PDCA vs CP resectable 0.887 0.872 0.879 0.877 0.875 52 PDCA vs non- all 0.880 0.893 0.886 0.898 0.908 pancreatic ctrl 52 PDCA vs non- low CA19-9 0.713 0.667 0.687 0.673 0.640 pancreatic ctrl 52 PDCA vs non- resectable 0.862 0.877 0.870 0.884 0.897 pancreatic ctrl 53 PDCA vs (CP + all 0.892 0.891 0.891 0.896 0.896 non-pancreatic ctrl) 53 PDCA vs (CP + low CA19-9 0.739 0.672 0.703 0.678 0.626 non-pancreatic ctrl) 53 PDCA vs (CP + resectable 0.875 0.874 0.875 0.880 0.880 non-pancreatic ctrl) 53 PDCA vs CP all 0.900 0.883 0.891 0.896 0.894 53 PDCA vs CP low CA19-9 0.804 0.717 0.757 0.738 0.693 53 PDCA vs CP resectable 0.889 0.870 0.880 0.885 0.883 53 PDCA vs non- all 0.881 0.892 0.887 0.897 0.907 pancreatic ctrl 53 PDCA vs non- low CA19-9 0.716 0.668 0.689 0.671 0.632 pancreatic ctrl 53 PDCA vs non- resectable 0.865 0.878 0.872 0.885 0.898 pancreatic ctrl 54 PDCA vs (CP + all 0.894 0.893 0.893 0.902 0.908 non-pancreatic ctrl) 54 PDCA vs (CP + low CA19-9 0.731 0.660 0.692 0.677 0.639 non-pancreatic ctrl) 54 PDCA vs (CP + resectable 0.875 0.874 0.874 0.885 0.892 non-pancreatic ctrl) 54 PDCA vs CP all 0.909 0.886 0.898 0.909 0.917 54 PDCA vs CP low CA19-9 0.808 0.704 0.752 0.749 0.727 54 PDCA vs CP resectable 0.892 0.865 0.879 0.891 0.901 54 PDCA vs non- all 0.865 0.887 0.876 0.889 0.902 pancreatic ctrl 54 PDCA vs non- low CA19-9 0.667 0.647 0.656 0.641 0.606 pancreatic ctrl 54 PDCA vs non- resectable 0.845 0.872 0.859 0.874 0.891 pancreatic ctrl 55 PDCA vs (CP + all 0.891 0.890 0.891 0.898 0.904 non-pancreatic ctrl) 55 PDCA vs (CP + low CA19-9 0.739 0.669 0.701 0.685 0.647 non-pancreatic ctrl) 55 PDCA vs (CP + resectable 0.872 0.871 0.872 0.880 0.887 non-pancreatic ctrl) 55 PDCA vs CP all 0.900 0.885 0.892 0.901 0.907 55 PDCA vs CP low CA19-9 0.802 0.717 0.756 0.750 0.722 55 PDCA vs CP resectable 0.887 0.869 0.878 0.888 0.896 55 PDCA vs non- all 0.878 0.888 0.884 0.895 0.906 pancreatic ctrl 55 PDCA vs non- low CA19-9 0.712 0.663 0.684 0.670 0.635 pancreatic ctrl 55 PDCA vs non- resectable 0.862 0.874 0.868 0.883 0.897 pancreatic ctrl 56 PDCA vs (CP + all 0.891 0.878 0.885 0.886 0.871 non-pancreatic ctrl) 56 PDCA vs (CP + low CA19-9 0.719 0.636 0.673 0.642 0.569 non-pancreatic ctrl) 56 PDCA vs (CP + resectable 0.885 0.870 0.878 0.879 0.863 non-pancreatic ctrl) 56 PDCA vs CP all 0.908 0.882 0.895 0.885 0.859 56 PDCA vs CP low CA19-9 0.817 0.704 0.756 0.702 0.598 56 PDCA vs CP resectable 0.909 0.881 0.894 0.884 0.856 56 PDCA vs non- all 0.880 0.885 0.883 0.886 0.877 pancreatic ctrl 56 PDCA vs non- low CA19-9 0.693 0.632 0.659 0.626 0.552 pancreatic ctrl 56 PDCA vs non- resectable 0.872 0.877 0.875 0.880 0.871 pancreatic ctrl 57 PDCA vs (CP + all 0.897 0.883 0.890 0.895 0.886 non-pancreatic ctrl) 57 PDCA vs (CP + low CA19-9 0.742 0.656 0.695 0.673 0.609 non-pancreatic ctrl) 57 PDCA vs (CP + resectable 0.891 0.876 0.884 0.890 0.880 non-pancreatic ctrl) 57 PDCA vs CP all 0.913 0.889 0.901 0.907 0.901 57 PDCA vs CP low CA19-9 0.830 0.734 0.778 0.767 0.710 57 PDCA vs CP resectable 0.912 0.887 0.899 0.907 0.901 57 PDCA vs non- all 0.885 0.884 0.885 0.889 0.882 pancreatic ctrl 57 PDCA vs non- low CA19-9 0.711 0.645 0.674 0.641 0.565 pancreatic ctrl 57 PDCA vs non- resectable 0.877 0.876 0.877 0.883 0.876 pancreatic ctrl 58 PDCA vs (CP + all 0.905 0.880 0.893 0.899 0.894 non-pancreatic ctrl) 58 PDCA vs (CP + low CA19-9 0.766 0.668 0.712 0.697 0.649 non-pancreatic ctrl) 58 PDCA vs (CP + resectable 0.893 0.864 0.879 0.886 0.880 non-pancreatic ctrl) 58 PDCA vs CP all 0.923 0.882 0.903 0.910 0.907 58 PDCA vs CP low CA19-9 0.867 0.755 0.806 0.800 0.761 58 PDCA vs CP resectable 0.915 0.869 0.892 0.900 0.896 58 PDCA vs non- all 0.894 0.887 0.890 0.895 0.889 pancreatic ctrl 58 PDCA vs non- low CA19-9 0.737 0.651 0.688 0.659 0.593 pancreatic ctrl 58 PDCA vs non- resectable 0.885 0.876 0.880 0.886 0.881 pancreatic ctrl 59 PDCA vs (CP + all 0.880 0.874 0.877 0.876 0.862 non-pancreatic ctrl) 59 PDCA vs (CP + low CA19-9 0.688 0.616 0.648 0.613 0.541 non-pancreatic ctrl) 59 PDCA vs (CP + resectable 0.870 0.863 0.867 0.866 0.850 non-pancreatic ctrl) 59 PDCA vs CP all 0.897 0.876 0.887 0.876 0.851 59 PDCA vs CP low CA19-9 0.797 0.683 0.735 0.677 0.577 59 PDCA vs CP resectable 0.892 0.870 0.881 0.869 0.840 59 PDCA vs non- all 0.867 0.881 0.874 0.878 0.871 pancreatic ctrl 59 PDCA vs non- low CA19-9 0.657 0.615 0.634 0.601 0.530 pancreatic ctrl 59 PDCA vs non- resectable 0.852 0.871 0.862 0.867 0.861 pancreatic ctrl 60 PDCA vs (CP + all 0.887 0.881 0.884 0.889 0.883 non-pancreatic ctrl) 60 PDCA vs (CP + low CA19-9 0.702 0.620 0.657 0.634 0.578 non-pancreatic ctrl) 60 PDCA vs (CP + resectable 0.877 0.870 0.873 0.879 0.873 non-pancreatic ctrl) 60 PDCA vs CP all 0.907 0.879 0.892 0.891 0.880 60 PDCA vs CP low CA19-9 0.800 0.668 0.729 0.696 0.629 60 PDCA vs CP resectable 0.899 0.867 0.883 0.881 0.869 60 PDCA vs non- all 0.861 0.880 0.870 0.875 0.870 pancreatic ctrl 60 PDCA vs non- low CA19-9 0.642 0.611 0.625 0.594 0.527 pancreatic ctrl 60 PDCA vs non- resectable 0.843 0.867 0.855 0.862 0.857 pancreatic ctrl 61 PDCA vs (CP + all 0.888 0.880 0.884 0.887 0.879 non-pancreatic ctrl) 61 PDCA vs (CP + low CA19-9 0.718 0.641 0.676 0.649 0.585 non-pancreatic ctrl) 61 PDCA vs (CP + resectable 0.880 0.871 0.876 0.880 0.871 non-pancreatic ctrl) 61 PDCA vs CP all 0.901 0.881 0.891 0.895 0.888 61 PDCA vs CP low CA19-9 0.813 0.713 0.759 0.742 0.683 61 PDCA vs CP resectable 0.897 0.876 0.886 0.892 0.885 61 PDCA vs non- all 0.874 0.883 0.879 0.883 0.879 pancreatic ctrl 61 PDCA vs non- low CA19-9 0.684 0.633 0.655 0.623 0.552 pancreatic ctrl 61 PDCA vs non- resectable 0.864 0.874 0.870 0.876 0.873 pancreatic ctrl 62 PDCA vs (CP + all 0.892 0.883 0.888 0.894 0.892 non-pancreatic ctrl) 62 PDCA vs (CP + low CA19-9 0.719 0.634 0.672 0.654 0.601 non-pancreatic ctrl) 62 PDCA vs (CP + resectable 0.881 0.872 0.877 0.885 0.883 non-pancreatic ctrl) 62 PDCA vs CP all 0.912 0.884 0.898 0.908 0.912 62 PDCA vs CP low CA19-9 0.818 0.699 0.754 0.752 0.717 62 PDCA vs CP resectable 0.902 0.871 0.887 0.899 0.903 62 PDCA vs non- all 0.861 0.879 0.870 0.876 0.874 pancreatic ctrl 62 PDCA vs non- low CA19-9 0.646 0.619 0.631 0.600 0.532 pancreatic ctrl 62 PDCA vs non- resectable 0.846 0.868 0.857 0.865 0.864 pancreatic ctrl 63 PDCA vs (CP + all 0.882 0.874 0.878 0.881 0.875 non-pancreatic ctrl) 63 PDCA vs (CP + low CA19-9 0.700 0.618 0.655 0.631 0.574 non-pancreatic ctrl) 63 PDCA vs (CP + resectable 0.870 0.861 0.866 0.869 0.862 non-pancreatic ctrl) 63 PDCA vs CP all 0.901 0.880 0.890 0.886 0.873 63 PDCA vs CP low CA19-9 0.805 0.694 0.745 0.708 0.635 63 PDCA vs CP resectable 0.894 0.871 0.882 0.878 0.864 63 PDCA vs non- all 0.869 0.881 0.875 0.880 0.874 pancreatic ctrl 63 PDCA vs non- low CA19-9 0.668 0.618 0.640 0.610 0.542 pancreatic ctrl 63 PDCA vs non- resectable 0.856 0.870 0.863 0.869 0.864 pancreatic ctrl 64 PDCA vs (CP + all 0.888 0.879 0.883 0.890 0.888 non-pancreatic ctrl) 64 PDCA vs (CP + low CA19-9 0.720 0.637 0.674 0.658 0.608 non-pancreatic ctrl) 64 PDCA vs (CP + resectable 0.877 0.867 0.872 0.880 0.879 non-pancreatic ctrl) 64 PDCA vs CP all 0.903 0.884 0.893 0.902 0.904 64 PDCA vs CP low CA19-9 0.813 0.716 0.761 0.758 0.721 64 PDCA vs CP resectable 0.897 0.876 0.886 0.897 0.900 64 PDCA vs non- all 0.873 0.880 0.877 0.882 0.879 pancreatic ctrl 64 PDCA vs non- low CA19-9 0.684 0.631 0.654 0.624 0.556 pancreatic ctrl 64 PDCA vs non- resectable 0.861 0.870 0.866 0.873 0.871 pancreatic ctrl 65 PDCA vs (CP + all 0.892 0.874 0.883 0.888 0.884 non-pancreatic ctrl) 65 PDCA vs (CP + low CA19-9 0.735 0.650 0.688 0.670 0.623 non-pancreatic ctrl) 65 PDCA vs (CP + resectable 0.877 0.856 0.867 0.873 0.868 non-pancreatic ctrl) 65 PDCA vs CP all 0.909 0.876 0.893 0.899 0.897 65 PDCA vs CP low CA19-9 0.842 0.733 0.782 0.773 0.735 65 PDCA vs CP resectable 0.896 0.859 0.878 0.885 0.882 65 PDCA vs non- all 0.880 0.883 0.882 0.886 0.882 pancreatic ctrl 65 PDCA vs non- low CA19-9 0.697 0.632 0.661 0.632 0.570 pancreatic ctrl 65 PDCA vs non- resectable 0.864 0.868 0.866 0.872 0.869 pancreatic ctrl 66 PDCA vs (CP + all 0.901 0.879 0.890 0.898 0.899 non-pancreatic ctrl) 66 PDCA vs (CP + low CA19-9 0.751 0.651 0.695 0.686 0.648 non-pancreatic ctrl) 66 PDCA vs (CP + resectable 0.884 0.858 0.871 0.881 0.882 non-pancreatic ctrl) 66 PDCA vs CP all 0.921 0.882 0.902 0.913 0.919 66 PDCA vs CP low CA19-9 0.858 0.734 0.790 0.793 0.773 66 PDCA vs CP resectable 0.907 0.861 0.884 0.896 0.902 66 PDCA vs non- all 0.877 0.883 0.881 0.886 0.885 pancreatic ctrl 66 PDCA vs non- low CA19-9 0.693 0.635 0.661 0.634 0.576 pancreatic ctrl 66 PDCA vs non- resectable 0.862 0.869 0.866 0.873 0.873 pancreatic ctrl 67 PDCA vs (CP + all 0.894 0.874 0.884 0.892 0.893 non-pancreatic ctrl) 67 PDCA vs (CP + low CA19-9 0.745 0.652 0.693 0.683 0.646 non-pancreatic ctrl) 67 PDCA vs (CP + resectable 0.877 0.854 0.866 0.875 0.875 non-pancreatic ctrl) 67 PDCA vs CP all 0.914 0.881 0.898 0.907 0.912 67 PDCA vs CP low CA19-9 0.854 0.746 0.795 0.796 0.772 67 PDCA vs CP resectable 0.901 0.864 0.883 0.893 0.898 67 PDCA vs non- all 0.884 0.882 0.883 0.888 0.885 pancreatic ctrl 67 PDCA vs non- low CA19-9 0.714 0.639 0.672 0.645 0.584 pancreatic ctrl 67 PDCA vs non- resectable 0.870 0.868 0.869 0.876 0.873 pancreatic ctrl 68 PDCA vs (CP + all 0.891 0.881 0.886 0.883 0.866 non-pancreatic ctrl) 68 PDCA vs (CP + low CA19-9 0.723 0.645 0.680 0.639 0.558 non-pancreatic ctrl) 68 PDCA vs (CP + resectable 0.880 0.869 0.875 0.872 0.852 non-pancreatic ctrl) 68 PDCA vs CP all 0.903 0.875 0.889 0.874 0.844 68 PDCA vs CP low CA19-9 0.809 0.700 0.750 0.684 0.573 68 PDCA vs CP resectable 0.903 0.873 0.887 0.872 0.838 68 PDCA vs non- all 0.873 0.884 0.878 0.883 0.877 pancreatic ctrl 68 PDCA vs non- low CA19-9 0.675 0.633 0.651 0.620 0.550 pancreatic ctrl 68 PDCA vs non- resectable 0.861 0.874 0.868 0.874 0.869 pancreatic ctrl 69 PDCA vs (CP + all 0.896 0.884 0.890 0.893 0.884 non-pancreatic ctrl) 69 PDCA vs (CP + low CA19-9 0.736 0.658 0.694 0.667 0.602 non-pancreatic ctrl) 69 PDCA vs (CP + resectable 0.886 0.873 0.880 0.883 0.873 non-pancreatic ctrl) 69 PDCA vs CP all 0.907 0.883 0.894 0.899 0.891 69 PDCA vs CP low CA19-9 0.814 0.724 0.765 0.748 0.687 69 PDCA vs CP resectable 0.903 0.877 0.890 0.895 0.887 69 PDCA vs non- all 0.878 0.882 0.880 0.886 0.881 pancreatic ctrl 69 PDCA vs non- low CA19-9 0.697 0.644 0.667 0.637 0.562 pancreatic ctrl 69 PDCA vs non- resectable 0.869 0.874 0.872 0.879 0.874 pancreatic ctrl 70 PDCA vs (CP + all 0.898 0.878 0.888 0.892 0.887 non-pancreatic ctrl) 70 PDCA vs (CP + low CA19-9 0.749 0.664 0.703 0.683 0.635 non-pancreatic ctrl) 70 PDCA vs (CP + resectable 0.881 0.858 0.870 0.875 0.868 non-pancreatic ctrl) 70 PDCA vs CP all 0.914 0.876 0.895 0.900 0.896 70 PDCA vs CP low CA19-9 0.855 0.752 0.798 0.787 0.746 70 PDCA vs CP resectable 0.902 0.858 0.880 0.886 0.881 70 PDCA vs non- all 0.884 0.883 0.884 0.888 0.884 pancreatic ctrl 70 PDCA vs non- low CA19-9 0.717 0.647 0.677 0.647 0.582 pancreatic ctrl 70 PDCA vs non- resectable 0.870 0.869 0.870 0.876 0.873 pancreatic ctrl 71 PDCA vs (CP + all 0.887 0.873 0.880 0.887 0.888 non-pancreatic ctrl) 71 PDCA vs (CP + low CA19-9 0.731 0.650 0.686 0.672 0.635 non-pancreatic ctrl) 71 PDCA vs (CP + resectable 0.866 0.849 0.857 0.865 0.866 non-pancreatic ctrl) 71 PDCA vs CP all 0.902 0.875 0.888 0.896 0.901 71 PDCA vs CP low CA19-9 0.838 0.744 0.787 0.783 0.758 71 PDCA vs CP resectable 0.884 0.853 0.869 0.877 0.882 71 PDCA vs non- all 0.875 0.880 0.877 0.883 0.882 pancreatic ctrl 71 PDCA vs non- low CA19-9 0.699 0.638 0.665 0.637 0.577 pancreatic ctrl 71 PDCA vs non- resectable 0.857 0.863 0.860 0.868 0.867 pancreatic ctrl 72 PDCA vs (CP + all 0.879 0.876 0.878 0.873 0.856 non-pancreatic ctrl) 72 PDCA vs (CP + low CA19-9 0.692 0.626 0.656 0.609 0.528 non-pancreatic ctrl) 72 PDCA vs (CP + resectable 0.865 0.862 0.864 0.859 0.839 non-pancreatic ctrl) 72 PDCA vs CP all 0.893 0.873 0.883 0.866 0.836 72 PDCA vs CP low CA19-9 0.788 0.681 0.730 0.657 0.547 72 PDCA vs CP resectable 0.885 0.863 0.874 0.855 0.820 72 PDCA vs non- all 0.858 0.880 0.869 0.874 0.871 pancreatic ctrl 72 PDCA vs non- low CA19-9 0.637 0.616 0.625 0.594 0.528 pancreatic ctrl 72 PDCA vs non- resectable 0.839 0.866 0.853 0.860 0.857 pancreatic ctrl 73 PDCA vs (CP + all 0.888 0.884 0.886 0.888 0.881 non-pancreatic ctrl) 73 PDCA vs (CP + low CA19-9 0.710 0.633 0.668 0.638 0.577 non-pancreatic ctrl) 73 PDCA vs (CP + resectable 0.872 0.867 0.869 0.872 0.864 non-pancreatic ctrl) 73 PDCA vs CP all 0.903 0.877 0.890 0.885 0.871 73 PDCA vs CP low CA19-9 0.799 0.676 0.733 0.690 0.615 73 PDCA vs CP resectable 0.891 0.861 0.876 0.870 0.854 73 PDCA vs non- all 0.858 0.881 0.869 0.876 0.874 pancreatic ctrl 73 PDCA vs non- low CA19-9 0.639 0.619 0.628 0.600 0.536 pancreatic ctrl 73 PDCA vs non- resectable 0.837 0.865 0.851 0.861 0.859 pancreatic ctrl 74 PDCA vs (CP + all 0.882 0.877 0.879 0.879 0.871 non-pancreatic ctrl) 74 PDCA vs (CP + low CA19-9 0.704 0.629 0.662 0.629 0.566 non-pancreatic ctrl) 74 PDCA vs (CP + resectable 0.866 0.859 0.863 0.863 0.853 non-pancreatic ctrl) 74 PDCA vs CP all 0.895 0.874 0.885 0.876 0.859 74 PDCA vs CP low CA19-9 0.793 0.689 0.737 0.687 0.604 74 PDCA vs CP resectable 0.886 0.863 0.874 0.865 0.846 74 PDCA vs non- all 0.864 0.880 0.872 0.878 0.875 pancreatic ctrl 74 PDCA vs non- low CA19-9 0.659 0.624 0.639 0.610 0.544 pancreatic ctrl 74 PDCA vs non- resectable 0.847 0.866 0.857 0.864 0.861 pancreatic ctrl 75 PDCA vs (CP + all 0.886 0.881 0.883 0.885 0.876 non-pancreatic ctrl) 75 PDCA vs (CP + low CA19-9 0.712 0.644 0.674 0.643 0.578 non-pancreatic ctrl) 75 PDCA vs (CP + resectable 0.874 0.869 0.872 0.874 0.864 non-pancreatic ctrl) 75 PDCA vs CP all 0.892 0.874 0.883 0.885 0.876 75 PDCA vs CP low CA19-9 0.790 0.701 0.742 0.718 0.655 75 PDCA vs CP resectable 0.887 0.867 0.877 0.880 0.870 75 PDCA vs non- all 0.867 0.881 0.874 0.880 0.877 pancreatic ctrl 75 PDCA vs non- low CA19-9 0.667 0.631 0.647 0.616 0.547 pancreatic ctrl 75 PDCA vs non- resectable 0.854 0.871 0.863 0.871 0.869 pancreatic ctrl 76 PDCA vs (CP + all 0.892 0.887 0.889 0.895 0.893 non-pancreatic ctrl) 76 PDCA vs (CP + low CA19-9 0.723 0.646 0.681 0.660 0.606 non-pancreatic ctrl) 76 PDCA vs (CP + resectable 0.877 0.871 0.874 0.881 0.879 non-pancreatic ctrl) 76 PDCA vs CP all 0.904 0.880 0.892 0.901 0.903 76 PDCA vs CP low CA19-9 0.803 0.696 0.745 0.739 0.701 76 PDCA vs CP resectable 0.891 0.863 0.877 0.887 0.889 76 PDCA vs non- all 0.859 0.880 0.870 0.877 0.877 pancreatic ctrl 76 PDCA vs non- low CA19-9 0.645 0.625 0.634 0.607 0.542 pancreatic ctrl 76 PDCA vs non- resectable 0.844 0.868 0.856 0.866 0.867 pancreatic ctrl 77 PDCA vs (CP + all 0.885 0.879 0.882 0.888 0.886 non-pancreatic ctrl) 77 PDCA vs (CP + low CA19-9 0.716 0.643 0.676 0.655 0.605 non-pancreatic ctrl) 77 PDCA vs (CP + resectable 0.871 0.865 0.869 0.875 0.874 non-pancreatic ctrl) 77 PDCA vs CP all 0.894 0.878 0.886 0.893 0.895 77 PDCA vs CP low CA19-9 0.792 0.708 0.747 0.739 0.699 77 PDCA vs CP resectable 0.885 0.867 0.876 0.884 0.887 77 PDCA vs non- all 0.867 0.879 0.873 0.880 0.879 pancreatic ctrl 77 PDCA vs non- low CA19-9 0.674 0.633 0.650 0.623 0.558 pancreatic ctrl 77 PDCA vs non- resectable 0.855 0.869 0.862 0.871 0.872 pancreatic ctrl 78 PDCA vs (CP + all 0.885 0.873 0.879 0.883 0.879 non-pancreatic ctrl) 78 PDCA vs (CP + low CA19-9 0.721 0.648 0.681 0.659 0.611 non-pancreatic ctrl) 78 PDCA vs (CP + resectable 0.865 0.851 0.858 0.863 0.857 non-pancreatic ctrl) 78 PDCA vs CP all 0.896 0.867 0.882 0.886 0.882 78 PDCA vs CP low CA19-9 0.827 0.728 0.773 0.758 0.718 78 PDCA vs CP resectable 0.881 0.848 0.865 0.869 0.865 78 PDCA vs non- all 0.871 0.881 0.876 0.882 0.880 pancreatic ctrl 78 PDCA vs non- low CA19-9 0.681 0.633 0.654 0.625 0.566 pancreatic ctrl 78 PDCA vs non- resectable 0.852 0.864 0.859 0.866 0.865 pancreatic ctrl 79 PDCA vs (CP + all 0.897 0.880 0.889 0.896 0.898 non-pancreatic ctrl) 79 PDCA vs (CP + low CA19-9 0.748 0.660 0.699 0.686 0.649 non-pancreatic ctrl) 79 PDCA vs (CP + resectable 0.876 0.856 0.866 0.875 0.876 non-pancreatic ctrl) 79 PDCA vs CP all 0.911 0.876 0.894 0.903 0.909 79 PDCA vs CP low CA19-9 0.849 0.738 0.788 0.787 0.768 79 PDCA vs CP resectable 0.892 0.851 0.872 0.882 0.888 79 PDCA vs non- all 0.873 0.883 0.878 0.885 0.885 pancreatic ctrl 79 PDCA vs non- low CA19-9 0.689 0.640 0.661 0.634 0.577 pancreatic ctrl 79 PDCA vs non- resectable 0.853 0.864 0.859 0.867 0.868 pancreatic ctrl 80 PDCA vs (CP + all 0.899 0.882 0.891 0.898 0.897 non-pancreatic ctrl) 80 PDCA vs (CP + low CA19-9 0.738 0.652 0.690 0.678 0.634 non-pancreatic ctrl) 80 PDCA vs (CP + resectable 0.888 0.869 0.879 0.887 0.886 non-pancreatic ctrl) 80 PDCA vs CP all 0.916 0.884 0.900 0.902 0.895 80 PDCA vs CP low CA19-9 0.838 0.727 0.778 0.758 0.702 80 PDCA vs CP resectable 0.912 0.877 0.895 0.898 0.890 80 PDCA vs non- all 0.883 0.888 0.885 0.897 0.903 pancreatic ctrl 80 PDCA vs non- low CA19-9 0.699 0.644 0.668 0.659 0.619 pancreatic ctrl 80 PDCA vs non- resectable 0.871 0.877 0.874 0.888 0.896 pancreatic ctrl 81 PDCA vs (CP + all 0.903 0.886 0.894 0.902 0.900 non-pancreatic ctrl) 81 PDCA vs (CP + low CA19-9 0.752 0.666 0.705 0.692 0.642 non-pancreatic ctrl) 81 PDCA vs (CP + resectable 0.894 0.875 0.885 0.894 0.892 non-pancreatic ctrl) 81 PDCA vs CP all 0.917 0.888 0.902 0.913 0.915 81 PDCA vs CP low CA19-9 0.841 0.742 0.787 0.790 0.757 81 PDCA vs CP resectable 0.913 0.883 0.898 0.910 0.913 81 PDCA vs non- all 0.886 0.885 0.886 0.896 0.901 pancreatic ctrl 81 PDCA vs non- low CA19-9 0.711 0.648 0.675 0.661 0.615 pancreatic ctrl 81 PDCA vs non- resectable 0.877 0.875 0.876 0.889 0.896 pancreatic ctrl 82 PDCA vs (CP + all 0.910 0.882 0.896 0.906 0.908 non-pancreatic ctrl) 82 PDCA vs (CP + low CA19-9 0.776 0.677 0.721 0.716 0.683 non-pancreatic ctrl) 82 PDCA vs (CP + resectable 0.896 0.865 0.881 0.892 0.893 non-pancreatic ctrl) 82 PDCA vs CP all 0.929 0.883 0.906 0.918 0.923 82 PDCA vs CP low CA19-9 0.877 0.763 0.815 0.821 0.803 82 PDCA vs CP resectable 0.921 0.871 0.897 0.910 0.914 82 PDCA vs non- all 0.895 0.889 0.892 0.903 0.909 pancreatic ctrl 82 PDCA vs non- low CA19-9 0.734 0.658 0.691 0.680 0.642 pancreatic ctrl 82 PDCA vs non- resectable 0.883 0.877 0.880 0.893 0.902 pancreatic ctrl 83 PDCA vs (CP + all 0.895 0.883 0.889 0.902 0.912 non-pancreatic ctrl) 83 PDCA vs (CP + low CA19-9 0.723 0.635 0.673 0.674 0.657 non-pancreatic ctrl) 83 PDCA vs (CP + resectable 0.880 0.866 0.873 0.888 0.901 non-pancreatic ctrl) 83 PDCA vs CP all 0.917 0.883 0.900 0.912 0.921 83 PDCA vs CP low CA19-9 0.826 0.695 0.754 0.759 0.748 83 PDCA vs CP resectable 0.906 0.868 0.887 0.900 0.911 83 PDCA vs non- all 0.861 0.882 0.872 0.887 0.900 pancreatic ctrl 83 PDCA vs non- low CA19-9 0.642 0.620 0.630 0.627 0.602 pancreatic ctrl 83 PDCA vs non- resectable 0.840 0.866 0.853 0.872 0.888 pancreatic ctrl 84 PDCA vs (CP + all 0.889 0.879 0.884 0.894 0.900 non-pancreatic ctrl) 84 PDCA vs (CP + low CA19-9 0.720 0.637 0.674 0.669 0.641 non-pancreatic ctrl) 84 PDCA vs (CP + resectable 0.874 0.861 0.868 0.879 0.886 non-pancreatic ctrl) 84 PDCA vs CP all 0.906 0.881 0.894 0.899 0.900 84 PDCA vs CP low CA19-9 0.819 0.709 0.759 0.749 0.714 84 PDCA vs CP resectable 0.896 0.869 0.882 0.888 0.890 84 PDCA vs non- all 0.872 0.884 0.878 0.891 0.902 pancreatic ctrl 84 PDCA vs non- low CA19-9 0.676 0.632 0.651 0.645 0.618 pancreatic ctrl 84 PDCA vs non- resectable 0.854 0.868 0.861 0.877 0.891 pancreatic ctrl 85 PDCA vs (CP + all 0.891 0.882 0.887 0.894 0.893 non-pancreatic ctrl) 85 PDCA vs (CP + low CA19-9 0.728 0.651 0.685 0.669 0.621 non-pancreatic ctrl) 85 PDCA vs (CP + resectable 0.882 0.872 0.877 0.885 0.885 non-pancreatic ctrl) 85 PDCA vs CP all 0.904 0.882 0.893 0.902 0.902 85 PDCA vs CP low CA19-9 0.819 0.715 0.762 0.758 0.719 85 PDCA vs CP resectable 0.899 0.874 0.887 0.897 0.897 85 PDCA vs non- all 0.875 0.883 0.879 0.890 0.898 pancreatic ctrl 85 PDCA vs non- low CA19-9 0.680 0.634 0.654 0.641 0.600 pancreatic ctrl 85 PDCA vs non- resectable 0.861 0.870 0.866 0.879 0.890 pancreatic ctrl 86 PDCA vs (CP + all 0.896 0.884 0.890 0.901 0.908 non-pancreatic ctrl) 86 PDCA vs (CP + low CA19-9 0.729 0.639 0.679 0.675 0.644 non-pancreatic ctrl) 86 PDCA vs (CP + resectable 0.883 0.870 0.876 0.889 0.898 non-pancreatic ctrl) 86 PDCA vs CP all 0.918 0.886 0.902 0.917 0.930 86 PDCA vs CP low CA19-9 0.833 0.709 0.765 0.780 0.774 86 PDCA vs CP resectable 0.907 0.871 0.889 0.906 0.920 86 PDCA vs non- all 0.863 0.879 0.871 0.885 0.897 pancreatic ctrl 86 PDCA vs non- low CA19-9 0.648 0.621 0.633 0.625 0.591 pancreatic ctrl 86 PDCA vs non- resectable 0.845 0.864 0.855 0.872 0.887 pancreatic ctrl 87 PDCA vs (CP + all 0.890 0.879 0.885 0.894 0.900 non-pancreatic ctrl) 87 PDCA vs (CP + low CA19-9 0.726 0.643 0.680 0.673 0.639 non-pancreatic ctrl) 87 PDCA vs (CP + resectable 0.877 0.865 0.871 0.882 0.889 non-pancreatic ctrl) 87 PDCA vs CP all 0.905 0.883 0.894 0.906 0.913 87 PDCA vs CP low CA19-9 0.819 0.718 0.764 0.771 0.749 87 PDCA vs CP resectable 0.897 0.872 0.884 0.898 0.906 87 PDCA vs non- all 0.874 0.881 0.877 0.889 0.899 pancreatic ctrl 87 PDCA vs non- low CA19-9 0.682 0.633 0.654 0.644 0.608 pancreatic ctrl 87 PDCA vs non- resectable 0.859 0.867 0.863 0.878 0.890 pancreatic ctrl 88 PDCA vs (CP + all 0.894 0.876 0.885 0.895 0.898 non-pancreatic ctrl) 88 PDCA vs (CP + low CA19-9 0.741 0.656 0.694 0.687 0.656 non-pancreatic ctrl) 88 PDCA vs (CP + resectable 0.878 0.858 0.868 0.879 0.883 non-pancreatic ctrl) 88 PDCA vs CP all 0.912 0.877 0.895 0.906 0.911 88 PDCA vs CP low CA19-9 0.847 0.733 0.784 0.788 0.767 88 PDCA vs CP resectable 0.902 0.863 0.883 0.896 0.901 88 PDCA vs non- all 0.882 0.886 0.884 0.896 0.905 pancreatic ctrl 88 PDCA vs non- low CA19-9 0.700 0.642 0.667 0.657 0.625 pancreatic ctrl 88 PDCA vs non- resectable 0.865 0.870 0.868 0.882 0.893 pancreatic ctrl 89 PDCA vs (CP + all 0.903 0.880 0.892 0.905 0.914 non-pancreatic ctrl) 89 PDCA vs (CP + low CA19-9 0.757 0.656 0.701 0.703 0.685 non-pancreatic ctrl) 89 PDCA vs (CP + resectable 0.884 0.858 0.871 0.886 0.897 non-pancreatic ctrl) 89 PDCA vs CP all 0.928 0.883 0.906 0.922 0.937 89 PDCA vs CP low CA19-9 0.868 0.737 0.796 0.813 0.817 89 PDCA vs CP resectable 0.916 0.865 0.891 0.909 0.925 89 PDCA vs non- all 0.877 0.885 0.881 0.895 0.907 pancreatic ctrl 89 PDCA vs non- low CA19-9 0.687 0.637 0.659 0.652 0.627 pancreatic ctrl 89 PDCA vs non- resectable 0.857 0.867 0.862 0.878 0.893 pancreatic ctrl 90 PDCA vs (CP + all 0.897 0.877 0.887 0.899 0.907 non-pancreatic ctrl) 90 PDCA vs (CP + low CA19-9 0.754 0.659 0.701 0.700 0.679 non-pancreatic ctrl) 90 PDCA vs (CP + resectable 0.879 0.855 0.867 0.880 0.889 non-pancreatic ctrl) 90 PDCA vs CP all 0.917 0.880 0.899 0.912 0.923 90 PDCA vs CP low CA19-9 0.859 0.747 0.797 0.808 0.800 90 PDCA vs CP resectable 0.906 0.865 0.886 0.900 0.912 90 PDCA vs non- all 0.884 0.885 0.885 0.897 0.906 pancreatic ctrl 90 PDCA vs non- low CA19-9 0.712 0.645 0.674 0.665 0.635 pancreatic ctrl 90 PDCA vs non- resectable 0.867 0.867 0.867 0.882 0.893 pancreatic ctrl 91 PDCA vs (CP + all 0.886 0.878 0.882 0.888 0.889 non-pancreatic ctrl) 91 PDCA vs (CP + low CA19-9 0.704 0.631 0.663 0.649 0.608 non-pancreatic ctrl) 91 PDCA vs (CP + resectable 0.872 0.863 0.867 0.875 0.876 non-pancreatic ctrl) 91 PDCA vs CP all 0.902 0.879 0.891 0.891 0.884 91 PDCA vs CP low CA19-9 0.810 0.698 0.749 0.721 0.666 91 PDCA vs CP resectable 0.893 0.867 0.880 0.881 0.873 91 PDCA vs non- all 0.869 0.884 0.877 0.890 0.899 pancreatic ctrl 91 PDCA vs non- low CA19-9 0.662 0.627 0.642 0.635 0.605 pancreatic ctrl 91 PDCA vs non- resectable 0.851 0.870 0.861 0.877 0.889 pancreatic ctrl 92 PDCA vs (CP + all 0.902 0.880 0.891 0.900 0.901 non-pancreatic ctrl) 92 PDCA vs (CP + low CA19-9 0.762 0.675 0.714 0.704 0.670 non-pancreatic ctrl) 92 PDCA vs (CP + resectable 0.886 0.860 0.873 0.882 0.884 non-pancreatic ctrl) 92 PDCA vs CP all 0.918 0.875 0.897 0.908 0.911 92 PDCA vs CP low CA19-9 0.865 0.757 0.806 0.808 0.788 92 PDCA vs CP resectable 0.908 0.860 0.885 0.896 0.900 92 PDCA vs non- all 0.885 0.884 0.885 0.896 0.903 pancreatic ctrl 92 PDCA vs non- low CA19-9 0.717 0.651 0.679 0.667 0.631 pancreatic ctrl 92 PDCA vs non- resectable 0.872 0.870 0.871 0.885 0.894 pancreatic ctrl 93 PDCA vs (CP + all 0.894 0.881 0.888 0.891 0.887 non-pancreatic ctrl) 93 PDCA vs (CP + low CA19-9 0.731 0.654 0.688 0.665 0.611 non-pancreatic ctrl) 93 PDCA vs (CP + resectable 0.881 0.865 0.873 0.878 0.872 non-pancreatic ctrl) 93 PDCA vs CP all 0.911 0.879 0.895 0.893 0.881 93 PDCA vs CP low CA19-9 0.831 0.723 0.772 0.739 0.672 93 PDCA vs CP resectable 0.907 0.871 0.889 0.887 0.874 93 PDCA vs non- all 0.874 0.883 0.879 0.891 0.898 pancreatic ctrl 93 PDCA vs non- low CA19-9 0.682 0.639 0.658 0.647 0.609 pancreatic ctrl 93 PDCA vs non- resectable 0.860 0.870 0.865 0.880 0.890 pancreatic ctrl 94 PDCA vs (CP + all 0.900 0.885 0.893 0.899 0.896 non-pancreatic ctrl) 94 PDCA vs (CP + low CA19-9 0.747 0.668 0.704 0.686 0.634 non-pancreatic ctrl) 94 PDCA vs (CP + resectable 0.889 0.872 0.881 0.888 0.885 non-pancreatic ctrl) 94 PDCA vs CP all 0.912 0.883 0.897 0.906 0.908 94 PDCA vs CP low CA19-9 0.828 0.734 0.777 0.774 0.740 94 PDCA vs CP resectable 0.906 0.874 0.890 0.900 0.902 94 PDCA vs non- all 0.878 0.882 0.880 0.891 0.896 pancreatic ctrl 94 PDCA vs non- low CA19-9 0.694 0.643 0.665 0.650 0.604 pancreatic ctrl 94 PDCA vs non- resectable 0.869 0.872 0.871 0.884 0.892 pancreatic ctrl 95 PDCA vs (CP + all 0.886 0.875 0.881 0.889 0.892 non-pancreatic ctrl) 95 PDCA vs (CP + low CA19-9 0.727 0.655 0.687 0.675 0.644 non-pancreatic ctrl) 95 PDCA vs (CP + resectable 0.867 0.854 0.861 0.870 0.874 non-pancreatic ctrl) 95 PDCA vs CP all 0.901 0.870 0.886 0.896 0.900 95 PDCA vs CP low CA19-9 0.835 0.732 0.778 0.777 0.757 95 PDCA vs CP resectable 0.888 0.853 0.871 0.882 0.887 95 PDCA vs non- all 0.871 0.881 0.876 0.888 0.899 pancreatic ctrl 95 PDCA vs non- low CA19-9 0.678 0.634 0.653 0.642 0.613 pancreatic ctrl 95 PDCA vs non- resectable 0.851 0.864 0.858 0.872 0.886 pancreatic ctrl 96 PDCA vs (CP + all 0.900 0.882 0.891 0.903 0.913 non-pancreatic ctrl) 96 PDCA vs (CP + low CA19-9 0.759 0.667 0.707 0.706 0.689 non-pancreatic ctrl) 96 PDCA vs (CP + resectable 0.878 0.857 0.867 0.881 0.893 non-pancreatic ctrl) 96 PDCA vs CP all 0.916 0.876 0.896 0.912 0.926 96 PDCA vs CP low CA19-9 0.855 0.736 0.789 0.803 0.806 96 PDCA vs CP resectable 0.899 0.854 0.877 0.894 0.909 96 PDCA vs non- all 0.873 0.883 0.878 0.892 0.905 pancreatic ctrl 96 PDCA vs non- low CA19-9 0.683 0.642 0.660 0.654 0.628 pancreatic ctrl 96 PDCA vs non- resectable 0.852 0.865 0.859 0.875 0.891 pancreatic ctrl 97 PDCA vs (CP + all 0.892 0.876 0.884 0.894 0.902 non-pancreatic ctrl) 97 PDCA vs (CP + low CA19-9 0.746 0.664 0.700 0.695 0.673 non-pancreatic ctrl) 97 PDCA vs (CP + resectable 0.871 0.853 0.862 0.874 0.883 non-pancreatic ctrl) 97 PDCA vs CP all 0.905 0.874 0.890 0.902 0.913 97 PDCA vs CP low CA19-9 0.844 0.743 0.788 0.795 0.787 97 PDCA vs CP resectable 0.890 0.855 0.873 0.886 0.898 97 PDCA vs non- all 0.876 0.881 0.878 0.891 0.902 pancreatic ctrl 97 PDCA vs non- low CA19-9 0.696 0.642 0.665 0.657 0.628 pancreatic ctrl 97 PDCA vs non- resectable 0.858 0.864 0.861 0.876 0.890 pancreatic ctrl 98 PDCA vs (CP + all 0.881 0.877 0.879 0.882 0.880 non-pancreatic ctrl) 98 PDCA vs (CP + low CA19-9 0.699 0.635 0.663 0.637 0.587 non-pancreatic ctrl) 98 PDCA vs (CP + resectable 0.865 0.860 0.863 0.867 0.864 non-pancreatic ctrl) 98 PDCA vs CP all 0.897 0.874 0.885 0.880 0.868 98 PDCA vs CP low CA19-9 0.800 0.692 0.741 0.699 0.630 98 PDCA vs CP resectable 0.887 0.860 0.874 0.868 0.854 98 PDCA vs non- all 0.859 0.880 0.870 0.883 0.894 pancreatic ctrl 98 PDCA vs non- low CA19-9 0.642 0.621 0.630 0.621 0.591 pancreatic ctrl 98 PDCA vs non- resectable 0.838 0.864 0.851 0.868 0.882 pancreatic ctrl 99 PDCA vs (CP + all 0.893 0.885 0.889 0.900 0.909 non-pancreatic ctrl) 99 PDCA vs (CP + low CA19-9 0.728 0.647 0.683 0.676 0.652 non-pancreatic ctrl) 99 PDCA vs (CP + resectable 0.874 0.865 0.870 0.882 0.893 non-pancreatic ctrl) 99 PDCA vs CP all 0.911 0.880 0.896 0.903 0.909 99 PDCA vs CP low CA19-9 0.820 0.694 0.751 0.743 0.720 99 PDCA vs CP resectable 0.897 0.860 0.879 0.887 0.893 99 PDCA vs non- all 0.857 0.880 0.869 0.885 0.899 pancreatic ctrl 99 PDCA vs non- low CA19-9 0.640 0.623 0.630 0.628 0.603 pancreatic ctrl 99 PDCA vs non- resectable 0.834 0.862 0.848 0.868 0.885 pancreatic ctrl 100 PDCA vs (CP + all 0.886 0.878 0.882 0.889 0.892 non-pancreatic ctrl) 100 PDCA vs (CP + low CA19-9 0.717 0.641 0.674 0.659 0.622 non-pancreatic ctrl) 100 PDCA vs (CP + resectable 0.868 0.858 0.863 0.871 0.875 non-pancreatic ctrl) 100 PDCA vs CP all 0.900 0.876 0.888 0.889 0.886 100 PDCA vs CP low CA19-9 0.807 0.702 0.750 0.726 0.680 100 PDCA vs CP resectable 0.888 0.860 0.874 0.875 0.872 100 PDCA vs non- all 0.865 0.880 0.873 0.886 0.898 pancreatic ctrl 100 PDCA vs non- low CA19-9 0.664 0.630 0.645 0.638 0.611 pancreatic ctrl 100 PDCA vs non- resectable 0.846 0.864 0.855 0.872 0.887 pancreatic ctrl 101 PDCA vs (CP + all 0.889 0.882 0.886 0.891 0.890 non-pancreatic ctrl) 101 PDCA vs (CP + low CA19-9 0.723 0.652 0.684 0.663 0.613 non-pancreatic ctrl) 101 PDCA vs (CP + resectable 0.876 0.868 0.873 0.879 0.878 non-pancreatic ctrl) 101 PDCA vs CP all 0.896 0.876 0.886 0.893 0.891 101 PDCA vs CP low CA19-9 0.801 0.707 0.750 0.740 0.699 101 PDCA vs CP resectable 0.889 0.866 0.878 0.885 0.884 101 PDCA vs non- all 0.868 0.881 0.874 0.886 0.896 pancreatic ctrl 101 PDCA vs non- low CA19-9 0.668 0.634 0.649 0.635 0.596 pancreatic ctrl 101 PDCA vs non- resectable 0.854 0.869 0.862 0.876 0.889 pancreatic ctrl 102 PDCA vs (CP + all 0.896 0.886 0.891 0.902 0.909 non-pancreatic ctrl) 102 PDCA vs (CP + low CA19-9 0.735 0.650 0.688 0.681 0.649 non-pancreatic ctrl) 102 PDCA vs (CP + resectable 0.879 0.868 0.874 0.886 0.895 non-pancreatic ctrl) 102 PDCA vs CP all 0.911 0.881 0.896 0.910 0.921 102 PDCA vs CP low CA19-9 0.818 0.704 0.756 0.766 0.756 102 PDCA vs CP resectable 0.896 0.862 0.879 0.895 0.907 102 PDCA vs non- all 0.858 0.877 0.868 0.882 0.895 pancreatic ctrl 102 PDCA vs non- low CA19-9 0.639 0.622 0.630 0.623 0.590 pancreatic ctrl 102 PDCA vs non- resectable 0.840 0.864 0.852 0.870 0.887 pancreatic ctrl 103 PDCA vs (CP + all 0.889 0.882 0.886 0.894 0.899 non-pancreatic ctrl) 103 PDCA vs (CP + low CA19-9 0.727 0.652 0.686 0.674 0.637 non-pancreatic ctrl) 103 PDCA vs (CP + resectable 0.874 0.865 0.870 0.880 0.886 non-pancreatic ctrl) 103 PDCA vs CP all 0.899 0.879 0.889 0.899 0.906 103 PDCA vs CP low CA19-9 0.803 0.713 0.754 0.756 0.733 103 PDCA vs CP resectable 0.887 0.865 0.876 0.888 0.896 103 PDCA vs non- all 0.868 0.878 0.873 0.886 0.897 pancreatic ctrl 103 PDCA vs non- low CA19-9 0.675 0.633 0.651 0.641 0.607 pancreatic ctrl 103 PDCA vs non- resectable 0.854 0.866 0.860 0.876 0.889 pancreatic ctrl 104 PDCA vs (CP + all 0.902 0.879 0.891 0.899 0.900 non-pancreatic ctrl) 104 PDCA vs (CP + low CA19-9 0.772 0.673 0.718 0.706 0.667 non-pancreatic ctrl) 104 PDCA vs (CP + resectable 0.883 0.856 0.870 0.879 0.879 non-pancreatic ctrl) 104 PDCA vs CP all 0.922 0.873 0.898 0.894 0.883 104 PDCA vs CP low CA19-9 0.877 0.752 0.809 0.778 0.721 104 PDCA vs CP resectable 0.909 0.854 0.882 0.877 0.863 104 PDCA vs non- all 0.846 0.896 0.871 0.888 0.911 pancreatic ctrl 104 PDCA vs non- low CA19-9 0.703 0.730 0.719 0.713 0.705 pancreatic ctrl 104 PDCA vs non- resectable 0.813 0.873 0.843 0.863 0.890 pancreatic ctrl PDAC = pancreatic cancer; CP = chronic pancreatitis; ctrl = control) Columns: A: Sample set for subgroup analysis (all refers to the entire data set of pancreatic cancer, chronic pancreatitis, and non-pancreatic control samples) B: AUC result of pancreatic cancer relative to chronic pancreatitis C: AUC result of pancreatic cancer relative to non-pancreatic controls D: AUC result of pancreatic cancer relative to (chronic pancreatitis and non-pancreatic controls) E: AUC result of pancreatic cancer relative to all non-cancer subjects (chronic pancreatitis, non-pancreatic controls, diabetes group, non-diabetes group) F: AUC result of pancreatic cancer relative to diabetic subjects (from chronic pancreatitis, non-pancreatic controls, diabetes group)

EXAMPLE 6: CLASSIFICATION OF PATIENTS USING THE BIOMARKER PANEL

Log-Transformation and Scaling

[0230] Input data: [0231] Absolute concentration of analytes measured by LC-MS/MS: One value for each analyte and patient sample. [0232] Absolute concentration of CA19-9 determined by a commercially available radio immunoassay (RIA): One value per patient sample. [0233] Transform all input data by log.sub.10. The numerical value for CA19-9 (U/ml) is being treated in the same way as the peak area ratios of the analytes measured by LC-MS/MS. [0234] Scale the log.sub.10-transformed input data x by first subtracting an analyte-specific constant m.sub.i and then dividing by a analyte-specific constant s.sub.i, resulting in log.sub.10-transformed and scaled input data {circumflex over (x)}:

[00004]${\hat{x}}_i=\frac{x_i-m_i}{s_i}$

[0235] For example, scaling parameters for the panel 6 and panel 7 are listed in Tables 12-13.

TABLE-US-00013 TABLE 12 Example of scaling parameters of compounds used for the panel 6 Pancreatic cancer versus Pancreatic Pancreatic (chronic cancer cancer pancreatitis versus versus non- and non- chronic pancreatic pancreatic pancreatitis control control) Biomarker m.sub.l s.sub.l m.sub.l s.sub.l m.sub.l s.sub.l Proline 2.096 0.147 2.094 0.150 2.112 0.15 Ceramide (d18:1,C24:0) 1.238 0.174 1.231 0.155 1.248 0.165 Lyso- 0.611 0.265 0.597 0.257 0.633 0.26 phosphatidylethanolamine (C18:2) Sphingomyelin (35:1) 1.376 0.179 1.435 0.135 1.388 0.163 Sphingomyelin (d18:2,C17:0) 0.659 0.163 0.709 0.132 0.669 0.149 CA19-9 1.590 1.032 1.495 1.087 1.331 0.978

TABLE-US-00014 TABLE 13 Example of scaling parameters of compounds used for the panel 7 Pancreatic cancer Pancreatic Pancreatic versus (chronic cancer versus cancer versus pancreatitis and chronic non-pancreatic non-pancreatic pancreatitis control control) Biomarker m.sub.l s.sub.l m.sub.l s.sub.l m.sub.l s.sub.l Proline 2.096 0.147 2.094 0.150 2.112 0.150 Tryptophan 1.767 0.140 1.775 0.136 1.781 0.136 Ceramide 1.238 0.174 1.231 0.155 1.248 0.165 (d18:1,C24:0) Sphingomyelin 1.376 0.179 1.435 0.135 1.388 0.163 (35:1) Sphingomyelin 0.659 0.163 0.709 0.132 0.669 0.149 (d18:2,C17:0) CA19-9 1.590 1.032 1.495 1.087 1.331 0.978

Calculation of the Prediction Score

[0236] The prediction score is calculated for each patient based on the log.sub.10-transformed and scaled input data {circumflex over (x)} using analyte-specific weights .sub.i and bias .sub.0:

[00005]$p=\frac{1}{1+e^{-\left({}_0+{}_i^n.Math.{}_i.Math.{\hat{x}}_i\right)}}$

[0237] For example, weights parameters for the biomarker panels 6 and 7 are listed in Tables 14-15.

TABLE-US-00015 TABLE 14 Example of weight parameters of compounds used for the biomarker panel 6 and bias Pancreatic Pancreatic cancer Pancreatic cancer cancer versus versus non- versus (chronic chronic pancreatic pancreatitis and non- pancreatitis; control; Bias pancreatic control); Bias (.sub.0) = 0.017 (.sub.0) = 0.020 Bias (.sub.0) = 0.929 Biomarker .sub.l .sub.l .sub.l Proline 0.190 0.297 0.244 Ceramide (d18:1, C24:0) 0.320 0.194 0.249 Lysophosphatidylethanolamine 0.304 0.124 0.199 (C18:2) Sphingomyelin (35:1) 0.566 0.191 0.380 Sphingomyelin (d18:2, C17:0) 0.264 0.000 0.123 CA19-9 0.910 1.143 1.079

TABLE-US-00016 TABLE 15 Example of weight parameters of compounds used for the biomarker panel 7 and bias Pancreatic Pancreatic cancer cancer Pancreatic cancer versus versus non- versus (chronic chronic pancreatic pancreatitis and pancreatitis; control; non-pancreatic Bias (.sub.0) = Bias (.sub.0) = control); 0.009 0.021 Bias (.sub.0) = 0.927 Biomarker .sub.l .sub.l .sub.l Proline 0.206 0.318 0.272 Tryptophan 0.243 0.131 0.131 Ceramide 0.391 0.218 0.282 (d18:1, C24:0) Sphingomyelin (35:1) 0.597 0.200 0.371 Sphingomyelin 0.315 0.000 0.140 (d18:2, C17:0) CA19-9 0.971 1.198 1.094

[0238] The prediction score can be interpreted as the score that the patient is suffering from PDAC assuming a prevalence of the disease as in the analyzed data set. By adaptation of the bias accordingly, the prediction score can be applied to the targeted patient population with the apparent prevalence. Calculated prediction scores can take on any value between 0 and 1. By comparing the prediction score with a pre-defined cutoff a patient can be classified.

Determination of the Cutoff

[0239] Cutoff values were determined by using two different methods. First, a cutoff was determined at a fixed specificity of 85%. An alternative cutoff was determined with the Youden index method optimizing the accuracy. Both methods were applied on the entire data set or on males or females only, respectively. For example, the cutoff values for biomarker panels 6 and 7 are listed in Table 16.

TABLE-US-00017 TABLE 16 Cutoffs for the prediction score allowing a classification for biomarker panel 6 and biomarker panel 7 Females and males Females Males Spec Spec Spec Task Panel Youden 85% Youden 85% Youden 85% Pancreatic 7 0.362 0.332 0.377 0.418 0.362 0.292 cancer versus (chronic pancreatitis and non-pancreatic control) Pancreatic 7 0.568 0.502 0.568 0.742 0.466 0.466 cancer versus chronic pancreatitis Pancreatic 7 0.510 0.455 0.510 0.503 0.445 0.405 cancer versus non-pancreatic control Pancreatic 6 0.391 0.337 0.407 0.416 0.391 0.278 cancer versus (chronic pancreatitis and non-pancreatic control) Pancreatic 6 0.502 0.502 0.611 0.714 0.502 0.424 cancer versus chronic pancreatitis Pancreatic 6 0.523 0.457 0.581 0.503 0.425 0.423 cancer versus non-pancreatic control

Patient/Sample Classification

[0240] A positive or negative diagnostic outcome is obtained from comparison of the result (or prediction score) obtained for a sample with the cutoff value. A prediction score greater than or equal to the cutoff value is taken as positive diagnostic outcome, a prediction score smaller than the cutoff value is taken as negative diagnostic outcome.

EXAMPLE 7: FURTHER BIOMARKER PANELS

[0241] Two further biomarker panels (Panel no. 105 and 106) were generated by treating the sum of all representatives of one ontology class together as one feature for the logistic regression model, respectively.

[0242] More precisely, the sum of histidine, proline, and tryptophan constitutes one feature, the sum of sphingomyelin (d17:1,C16:0), sphingomyelin (d18:2,C17:0), sphingomyelin (35:1) and sphingomyelin (41:2) constitutes one feature, and the sum of ceramide (d18:1,C24:0), ceramide (d18:2,C24:0) constitutes one feature in both, Panel 105 and Panel 106.

[0243] Additionally, the ratio of lysophosphatidylethanolamine (C18:2) to phosphatidylethanolamine (C18:0,C22:6) was used as a feature in Panel 106.

[0244] Panels 105 and 106 are constituted as shown in Table 17, below:

TABLE-US-00018 TABLE 17 Panel Number Panel Composition 105 CA 19-9, [histidine + proline + tryptophan], [sphingomyelin (d17:1, C16:0) + sphingomyelin (d18:2, C17:0) + sphingomyelin (35:1) + sphingomyelin (41:2)], [ceramide (d18:1, C24:0) + ceramide (d18:2, C24:0)] 106 CA 19-9, [histidine + proline + tryptophan], [sphingomyelin (d17:1, C16:0) + sphingomyelin (d18:2, C17:0) + sphingomyelin (35:1) + sphingomyelin (41:2)], [ceramide (d18:1, C24:0) + ceramide (d18:2, C24:0)], [lysophosphatidylethanolamine (C18:2)/phosphatidylethanolamine (C18:0, C22:6)]

[0245] Performance/classification results for both of the panels are shown in Table 18, below.

TABLE-US-00019 TABLE 18 Subgroup performance of the diagnostic biomarker panels shown in Table 17, including diabetes and resectable pancreatic cancer (PDAC = pancreatic cancer; CP = chronic pancreatitis; ctrl = control) Panel Number Training of panel on A Cutoff B C D E F G 105 PDAC vs. CP all 0.4901 0.914 0.915 0.82 0.81 0.83 0.89 105 PDAC vs. Healthy all 0.4965 0.865 0.914 0.79 0.81 0.81 0.89 105 PDAC vs. (CP + non-pancreatic ctrl) all 0.3095 0.900 0.919 0.82 0.81 0.83 0.89 105 PDAC resectable vs. CP all 0.3582 0.904 0.918 0.81 0.81 0.86 0.83 105 PDAC resectable vs. Healthy all 0.3786 0.852 0.904 0.82 0.81 0.86 0.89 105 PDAC resectable vs. (CP + non- all 0.2065 0.890 0.923 0.84 0.81 0.86 0.83 pancreatic ctrl) 106 PDAC vs. CP all 0.4337 0.924 0.914 0.90 0.81 0.94 0.72 106 PDAC vs. Healthy all 0.4794 0.869 0.910 0.81 0.81 0.83 0.89 106 PDAC vs. (CP + non-pancreatic ctrl) all 0.2712 0.912 0.927 0.91 0.81 0.92 0.83 106 PDAC resectable vs. CP all 0.3305 0.918 0.920 0.91 0.81 0.94 0.83 106 PDAC resectable vs. Healthy all 0.3807 0.860 0.892 0.81 0.81 0.83 0.89 106 PDAC resectable vs. (CP + non- all 0.1917 0.890 0.926 0.88 0.81 0.89 0.89 pancreatic ctrl) 105 PDAC vs. CP resectable 0.4901 0.898 0.904 0.80 0.81 0.78 0.89 105 PDAC vs. Healthy resectable 0.4965 0.832 0.895 0.73 0.81 0.72 0.89 105 PDAC vs. (CP + non-pancreatic ctrl) resectable 0.3095 0.886 0.914 0.78 0.81 0.78 0.89 105 PDAC resectable vs. CP resectable 0.3582 0.890 0.920 0.80 0.81 0.83 0.83 105 PDAC resectable vs. Healthy resectable 0.3786 0.823 0.898 0.80 0.81 0.83 0.89 105 PDAC resectable vs. (CP + non- resectable 0.2065 0.878 0.924 0.83 0.81 0.83 0.83 pancreatic ctrl) 106 PDAC vs. CP resectable 0.4337 0.912 0.900 0.90 0.81 0.94 0.72 106 PDAC vs. Healthy resectable 0.4794 0.840 0.889 0.78 0.81 0.78 0.89 106 PDAC vs. (CP + non-pancreatic ctrl) resectable 0.2712 0.898 0.914 0.90 0.81 0.94 0.83 106 PDAC resectable vs. CP resectable 0.3305 0.897 0.902 0.90 0.81 0.94 0.83 106 PDAC resectable vs. Healthy resectable 0.3807 0.822 0.868 0.78 0.81 0.78 0.89 106 PDAC resectable vs. (CP + non- resectable 0.1917 0.876 0.922 0.88 0.81 0.89 0.89 pancreatic ctrl) A: Sample set for subgroup analysis (all refers to the entire data set of pancreatic cancer, chronic pancreatitis, and non-pancreatic control samples) B: AUC result of pancreatic cancer (PDAC) versus chronic pancreatitis C: AUC result of PDAC versus diabetic controls D: Sensitivity of PDAC versus chronic pancreatitis E: Specifity of PDAC versus chronic pancreatitis F: Sensitivity of PDAC versus diabetic controls G: Specifity of PDAC versus diabetic controls

EXAMPLE 8: REFINEMENT OF CLASSIFICATION OF PATIENTS USING THE BIOMARKER PANEL/ADAPTATION OF ALGORITHM

[0246] Five to seven percent of the population do not produce CA19-9 due to specific, inherited Lewis a/b antigen negativity (either homo-, or heterozygous). For these patients, CA19-9 always produces a negative test result regardless of whether the patient has cancer or not. The metabolic markers do not have the same problem. To address this issue, it was decided to train both, a logistic regression model including our metabolites and CA19-9, and an additional model using only the respective metabolites (without CA19-9). When optimizing the algorithm for a given panel to obtain a certain specificity, this approach also yields different cut-offs for the two models.

[0247] Accordingly, the following rule was used for patient classification: If the patient's CA19-9 value is above a certain threshold, the model including CA19-9 with the respective cutoff was used; otherwise, the model without CA19-9 with its specific cutoff was used. Since the two prediction scores generated by the two models are not directly comparable, calculation of a meaningful AUC would be possible by first aligning the scores in some way. However, calculation of Sensitivity and Specificity is directly possible, and is also an appropriate measure for the application in this case.

[0248] In our case the threshold used was a CA19-9 value of 2 U/ml.

[0249] The approach can be further refined by first training the model including CA19-9 only on patients which have a CA19-9 measurement above the threshold.

TABLE-US-00020 TABLE 19 Effect of using two different, CA 19-9-dependent models (two-model algorithm) per panel instead of just one on sensititvity and specificity; the positive groups are shown in the Training-column, respectively (i.e. PDAC or resectable PDAC): Panel Number Training of Panel on A B C D E F 1 PDAC vs. CP 88.3% 93.5% 79.7% 75.9% 81.0% 72.2% 2 PDAC vs. CP 89.6% 94.8% 79.7% 75.9% 75.9% 63.3% 3 PDAC vs. CP 88.3% 93.5% 82.3% 77.2% 77.2% 68.4% 4 PDAC vs. CP 88.3% 93.5% 79.7% 74.7% 78.5% 68.4% 5 PDAC vs. CP 88.3% 93.5% 82.3% 77.2% 77.2% 68.4% 6 PDAC vs. CP 88.3% 93.5% 81.0% 75.9% 74.7% 65.8% 7 PDAC vs. CP 88.3% 92.2% 82.3% 78.5% 78.5% 69.6% 8 PDAC vs. CP 89.6% 94.8% 79.7% 75.9% 78.5% 70.9% 9 PDAC vs. CP 90.9% 96.1% 79.7% 75.9% 70.9% 59.5% 10 PDAC vs. CP 90.9% 94.8% 81.0% 77.2% 73.4% 63.3% 11 PDAC vs. CP 90.9% 96.1% 82.3% 78.5% 72.2% 62.0% 12 PDAC vs. CP 87.0% 92.2% 83.5% 78.5% 83.5% 75.9% 13 PDAC vs. CP 89.6% 94.8% 81.0% 77.2% 78.5% 65.8% 14 PDAC vs. CP 87.0% 92.2% 81.0% 77.2% 81.0% 73.4% 15 PDAC vs. CP 89.6% 94.8% 77.2% 73.4% 74.7% 64.6% 16 PDAC vs. CP 87.0% 90.9% 82.3% 78.5% 81.0% 72.2% 17 PDAC vs. CP 84.4% 89.6% 81.0% 77.2% 79.7% 69.6% 18 PDAC vs. CP 87.0% 90.9% 77.2% 73.4% 77.2% 68.4% 19 PDAC vs. CP 84.4% 88.3% 82.3% 78.5% 84.8% 78.5% 20 PDAC vs. CP 83.1% 88.3% 79.7% 74.7% 82.3% 72.2% 21 PDAC vs. CP 84.4% 88.3% 78.5% 74.7% 84.8% 78.5% 22 PDAC vs. CP 87.0% 90.9% 78.5% 75.9% 77.2% 68.4% 23 PDAC vs. CP 85.7% 89.6% 79.7% 77.2% 78.5% 69.6% 24 PDAC vs. CP 87.0% 89.6% 74.7% 72.2% 79.7% 69.6% 25 PDAC vs. CP 87.0% 90.9% 74.7% 72.2% 78.5% 68.4% 26 PDAC vs. CP 87.0% 92.2% 78.5% 74.7% 82.3% 74.7% 27 PDAC vs. CP 85.7% 89.6% 77.2% 74.7% 79.7% 72.2% 28 PDAC vs. CP 84.4% 89.6% 75.9% 74.7% 83.5% 75.9% 29 PDAC vs. CP 84.4% 88.3% 75.9% 73.4% 83.5% 77.2% 30 PDAC vs. CP 87.0% 90.9% 82.3% 78.5% 75.9% 67.1% 31 PDAC vs. CP 88.3% 90.9% 78.5% 75.9% 77.2% 69.6% 32 PDAC vs. CP 88.3% 90.9% 81.0% 75.9% 73.4% 64.6% 33 PDAC vs. CP 89.6% 93.5% 81.0% 77.2% 74.7% 65.8% 34 PDAC vs. CP 87.0% 92.2% 79.7% 75.9% 78.5% 67.1% 35 PDAC vs. CP 84.4% 88.3% 78.5% 74.7% 81.0% 70.9% 36 PDAC vs. CP 85.7% 88.3% 83.5% 79.7% 82.3% 73.4% 37 PDAC vs. CP 88.3% 92.2% 81.0% 78.5% 81.0% 74.7% 38 PDAC vs. CP 88.3% 93.5% 83.5% 79.7% 74.7% 65.8% 39 PDAC vs. CP 89.6% 94.8% 78.5% 75.9% 73.4% 63.3% 40 PDAC vs. CP 88.3% 93.5% 83.5% 79.7% 77.2% 69.6% 41 PDAC vs. CP 85.7% 89.6% 82.3% 77.2% 81.0% 70.9% 42 PDAC vs. CP 85.7% 90.9% 81.0% 77.2% 75.9% 65.8% 43 PDAC vs. CP 90.9% 93.5% 86.1% 83.5% 78.5% 67.1% 44 PDAC vs. CP 90.9% 93.5% 79.7% 77.2% 77.2% 65.8% 45 PDAC vs. CP 87.0% 92.2% 78.5% 73.4% 75.9% 67.1% 46 PDAC vs. CP 90.9% 93.5% 81.0% 78.5% 81.0% 70.9% 47 PDAC vs. CP 90.9% 93.5% 81.0% 77.2% 77.2% 65.8% 48 PDAC vs. CP 90.9% 93.5% 82.3% 79.7% 83.5% 72.2% 49 PDAC vs. CP 90.9% 93.5% 79.7% 75.9% 82.3% 72.2% 50 PDAC vs. CP 84.4% 88.3% 82.3% 78.5% 83.5% 77.2% 51 PDAC vs. CP 83.1% 88.3% 79.7% 75.9% 77.2% 67.1% 52 PDAC vs. CP 84.4% 89.6% 82.3% 77.2% 78.5% 70.9% 53 PDAC vs. CP 88.3% 93.5% 82.3% 78.5% 74.7% 65.8% 54 PDAC vs. CP 88.3% 93.5% 79.7% 77.2% 75.9% 67.1% 55 PDAC vs. CP 85.7% 90.9% 78.5% 73.4% 81.0% 73.4% 56 PDAC vs. CP 87.0% 92.2% 77.2% 72.2% 78.5% 70.9% 57 PDAC vs. CP 88.3% 93.5% 79.7% 75.9% 74.7% 65.8% 58 PDAC vs. CP 88.3% 92.2% 82.3% 79.7% 77.2% 65.8% 59 PDAC vs. CP 85.7% 89.6% 81.0% 77.2% 81.0% 72.2% 60 PDAC vs. CP 85.7% 89.6% 78.5% 75.9% 79.7% 68.4% 61 PDAC vs. CP 88.3% 93.5% 79.7% 75.9% 77.2% 68.4% 62 PDAC vs. CP 88.3% 92.2% 77.2% 74.7% 81.0% 69.6% 63 PDAC vs. CP 87.0% 92.2% 77.2% 73.4% 81.0% 72.2% 64 PDAC vs. CP 87.0% 92.2% 77.2% 73.4% 78.5% 70.9% 65 PDAC vs. CP 88.3% 93.5% 79.7% 77.2% 77.2% 67.1% 66 PDAC vs. CP 89.6% 93.5% 81.0% 78.5% 81.0% 72.2% 67 PDAC vs. CP 88.3% 93.5% 78.5% 75.9% 77.2% 67.1% 68 PDAC vs. CP 85.7% 90.9% 78.5% 74.7% 82.3% 75.9% 69 PDAC vs. CP 87.0% 93.5% 78.5% 74.7% 77.2% 67.1% 70 PDAC vs. CP 88.3% 93.5% 75.9% 74.7% 77.2% 69.6% 71 PDAC vs. CP 87.0% 90.9% 79.7% 78.5% 79.7% 72.2% 72 PDAC vs. CP 85.7% 89.6% 78.5% 74.7% 82.3% 74.7% 73 PDAC vs. CP 85.7% 90.9% 79.7% 77.2% 81.0% 70.9% 74 PDAC vs. CP 84.4% 89.6% 77.2% 73.4% 82.3% 74.7% 75 PDAC vs. CP 87.0% 92.2% 79.7% 75.9% 79.7% 70.9% 76 PDAC vs. CP 87.0% 92.2% 75.9% 73.4% 79.7% 70.9% 77 PDAC vs. CP 85.7% 90.9% 77.2% 73.4% 83.5% 75.9% 78 PDAC vs. CP 88.3% 93.5% 78.5% 77.2% 79.7% 70.9% 79 PDAC vs. CP 88.3% 93.5% 77.2% 75.9% 79.7% 70.9% 80 PDAC vs. CP 88.3% 93.5% 82.3% 78.5% 74.7% 64.6% 81 PDAC vs. CP 89.6% 93.5% 79.7% 75.9% 75.9% 65.8% 82 PDAC vs. CP 90.9% 93.5% 82.3% 79.7% 74.7% 63.3% 83 PDAC vs. CP 87.0% 90.9% 82.3% 78.5% 77.2% 67.1% 84 PDAC vs. CP 88.3% 93.5% 82.3% 75.9% 75.9% 65.8% 85 PDAC vs. CP 87.0% 92.2% 83.5% 79.7% 77.2% 65.8% 86 PDAC vs. CP 88.3% 93.5% 79.7% 75.9% 77.2% 65.8% 87 PDAC vs. CP 88.3% 93.5% 78.5% 74.7% 74.7% 65.8% 88 PDAC vs. CP 90.9% 94.8% 83.5% 79.7% 73.4% 62.0% 89 PDAC vs. CP 89.6% 92.2% 79.7% 77.2% 72.2% 59.5% 90 PDAC vs. CP 90.9% 93.5% 81.0% 77.2% 77.2% 67.1% 91 PDAC vs. CP 87.0% 90.9% 82.3% 78.5% 74.7% 65.8% 92 PDAC vs. CP 90.9% 94.8% 81.0% 78.5% 74.7% 64.6% 93 PDAC vs. CP 84.4% 89.6% 79.7% 75.9% 78.5% 69.6% 94 PDAC vs. CP 89.6% 96.1% 81.0% 77.2% 75.9% 67.1% 95 PDAC vs. CP 89.6% 93.5% 79.7% 77.2% 75.9% 65.8% 96 PDAC vs. CP 89.6% 92.2% 78.5% 74.7% 75.9% 64.6% 97 PDAC vs. CP 89.6% 94.8% 75.9% 73.4% 78.5% 69.6% 98 PDAC vs. CP 83.1% 87.0% 82.3% 78.5% 81.0% 74.7% 99 PDAC vs. CP 85.7% 90.9% 79.7% 75.9% 78.5% 68.4% 100 PDAC vs. CP 85.7% 90.9% 81.0% 77.2% 81.0% 70.9% 101 PDAC vs. CP 88.3% 93.5% 82.3% 78.5% 77.2% 68.4% 102 PDAC vs. CP 85.7% 90.9% 83.5% 79.7% 77.2% 67.1% 103 PDAC vs. CP 87.0% 92.2% 81.0% 77.2% 77.2% 69.6% 104 PDAC vs. CP 89.6% 94.8% 81.0% 77.2% 75.9% 65.8% 105 PDAC vs. CP 84.4% 88.3% 86.1% 83.5% 86.1% 77.2% 105 PDAC vs. Healthy 81.8% 84.4% 82.3% 78.5% 93.7% 91.1% 105 PDAC vs. (CP + non-pancreatic ctrl) 83.1% 87.0% 86.1% 83.5% 91.1% 84.8% 105 PDAC resectable vs. CP 83.1% 87.0% 87.3% 84.8% 84.8% 77.2% 105 PDAC resectable vs. Healthy 83.1% 85.7% 81.0% 78.5% 92.4% 88.6% 105 PDAC resectable vs. (CP + non- 84.4% 87.0% 82.3% 78.5% 91.1% 83.5% pancreatic ctrl) 106 PDAC vs. CP 88.3% 93.5% 87.3% 83.5% 83.5% 73.4% 106 PDAC vs. Healthy 85.7% 89.6% 77.2% 73.4% 88.6% 83.5% 106 PDAC vs. (CP + non-pancreatic ctrl) 87.0% 92.2% 86.1% 83.5% 84.8% 77.2% 106 PDAC resectable vs. CP 87.0% 92.2% 88.6% 86.1% 83.5% 73.4% 106 PDAC resectable vs. Healthy 83.1% 87.0% 78.5% 74.7% 89.9% 84.8% 106 PDAC resectable vs. (CP + non- 85.7% 89.6% 87.3% 86.1% 89.9% 82.3% pancreatic ctrl) A: Sensitivity observed with same model for all samples B: Sensitivity observed with two-model algorithm according to CA19-9 level C: Specificity observed with same model for all samples, PDAC versus chronic pancreatitis D: Specificity observed with two-model algorithm according to CA19-9 level, versus chronic pancreatitis E: Specificity observed with same model for all samples, versus non-pancreatic control F: Specificity observed with two-model algorithm according to CA19-9 level, versus non-pancreatic control

EXAMPLE 9 ANALYSIS OF SPECIFICITY AGAINST OTHER DISEASES

[0250] In order to analyze the biomarker specificity against other diseases, two studies were carried out in addition to the studies described in Example 1 (referred to as PDAC study and Diabetes study in FIGS. 1 to 5 and Table 20). First, a human EDTA plasma sample collection from 97 fasted treatment-nave lung cancer patients (males and females, age 47-79 years) was analyzed comprising 20 small cell lung cancer cases, 52 non-small cell lung cancer (NSCLC) adeno carcinoma cases, 18 NSCLC squamous cell carcinoma cases, 4 NSCLC large cell carcinoma cases, and 3 NSCLC (not further characterized) cases (referred to as Lung cancer study in FIGS. 1 to 5 and Table 20). Second, from a human EDTA plasma sample collection from a prostate cancer diagnosis study, 445 samples were selected according to self-reported comorbidities from fasted male prostate cancer and control patients and analysed (referred to as Other comorbidity study in FIGS. 1 to 5 and Table 20).

[0251] All patients or their legal representatives gave their written informed consent and the local ethics review boards approved the protocol. After blood drawing and centrifugation according to the blood draw tube manufacturer's instruction, EDTA plasma was collected in Eppendorf tubes and stored at 80 C. for further analysis.

[0252] The resulting overall set of samples for the analysis of specificity against other diseases/comorbidities was as shown in Table 20, below:

TABLE-US-00021 TABLE 20 overall set of samples for the analysis of specificity against other diseases Group number Study Group name n 1 PDAC study Pancreatic cancer 77 2 PDAC study Chronic pancreatitis 79 3 PDAC study Non-pancreatic control (thyroid resections and hernia repair) 79 4 Diabetes study Diabetes and other comorbidities 51 5 Diabetes study Other comorbidities, but no diabetes 50 6 Lung cancer study Small cell lung cancer 20 7 Lung cancer study Non-small cell lung cancer (NSCLC) 3 8 Lung cancer study NSCLC adenocarcinoma 52 9 Lung cancer study NSCLC large cell carcinoma 4 10 Lung cancer study NSCLC squamous cell carcinoma 18 11 Other comorbidities Diabetes and dyslipidemia, most also hypertension 12 study 12 Other comorbidities Diabetes but no dyslipidemia, more than half also 34 study hypertension 13 Other comorbidities No comorbidities, age 62 or younger 42 study 14 Other comorbidities No comorbidities, age 63 or older 29 study 15 Other comorbidities Prostate cancer 48 study 16 Other comorbidities Cardiovascular diseases 49 study 17 Other comorbidities Chronic obstructive pulmonary disease, half also 16 study hypertension 18 Other comorbidities Dyslipidemia but no diabetes, more than half also 36 study hypertension 19 Other comorbidities Hypertension with other comorbidities, but no diabetes or 62 study dyslipidemia 20 Other comorbidities Hypertension only 37 study 21 Other comorbidities Other comorbidities, age 62 or younger 35 study 22 Other comorbidities Other comorbidities, age 63 or older 32 study 23 Other comorbidities Thyroid disorders 13 study

[0253] Using the above-described samples in order to assess the disease-specificity of the biomarker panels of the invention, it was found that the classification score showed a remarkably high specificity, also with regard to the panels of the invention in comparison to the CA19-9 as a single marker (see FIGS. 2 to 5). Results of this analysis are shown for all panels of the invention in Table 21, below. Also, prediction scores without CA19-9 were comparable in predictive value to CA19-9 as a single marker, as shown in representative examples in FIGS. 2, 3A, 4A, and 5A.

TABLE-US-00022 TABLE 21 Median of prediction score for the disease-/comorbidity groups shown in Table 20. Panel Training of panel Median of prediction score for group number No. on 1 2 3 4 5 6 7 8 9 10 11 1 PDAC vs CP 0.81 0.20 0.30 0.27 0.23 0.48 0.31 0.32 0.37 0.35 0.16 2 PDAC vs CP 0.80 0.18 0.28 0.23 0.22 0.45 0.33 0.33 0.37 0.29 0.15 3 PDAC vs CP 0.80 0.21 0.28 0.28 0.23 0.39 0.20 0.29 0.34 0.30 0.13 4 PDAC vs CP 0.79 0.19 0.28 0.32 0.27 0.44 0.33 0.35 0.34 0.36 0.19 5 PDAC vs CP 0.80 0.21 0.28 0.28 0.23 0.39 0.20 0.29 0.34 0.30 0.13 6 PDAC vs CP 0.79 0.20 0.27 0.28 0.23 0.40 0.21 0.30 0.35 0.31 0.13 7 PDAC vs CP 0.81 0.19 0.26 0.23 0.18 0.49 0.30 0.31 0.36 0.32 0.14 8 PDAC vs CP 0.80 0.18 0.26 0.25 0.21 0.44 0.21 0.27 0.34 0.32 0.12 9 PDAC vs CP 0.80 0.18 0.28 0.21 0.19 0.45 0.26 0.28 0.35 0.27 0.14 10 PDAC vs CP 0.80 0.18 0.27 0.20 0.19 0.44 0.26 0.29 0.35 0.28 0.13 11 PDAC vs CP 0.81 0.15 0.24 0.29 0.28 0.47 0.35 0.34 0.32 0.33 0.18 12 PDAC vs CP 0.80 0.23 0.29 0.28 0.23 0.41 0.34 0.33 0.38 0.32 0.19 13 PDAC vs CP 0.79 0.21 0.29 0.24 0.23 0.47 0.36 0.33 0.38 0.26 0.20 14 PDAC vs CP 0.78 0.20 0.27 0.37 0.30 0.41 0.36 0.34 0.34 0.35 0.20 15 PDAC vs CP 0.82 0.22 0.25 0.30 0.25 0.38 0.23 0.30 0.35 0.29 0.15 16 PDAC vs CP 0.80 0.21 0.28 0.28 0.25 0.46 0.29 0.30 0.27 0.36 0.13 17 PDAC vs CP 0.83 0.21 0.27 0.26 0.25 0.33 0.25 0.23 0.23 0.27 0.14 18 PDAC vs CP 0.79 0.22 0.27 0.26 0.22 0.46 0.28 0.30 0.32 0.34 0.13 19 PDAC vs CP 0.79 0.25 0.28 0.28 0.23 0.36 0.32 0.28 0.29 0.31 0.18 20 PDAC vs CP 0.81 0.24 0.27 0.27 0.25 0.28 0.28 0.24 0.25 0.24 0.16 21 PDAC vs CP 0.77 0.22 0.28 0.28 0.24 0.42 0.31 0.31 0.34 0.31 0.15 22 PDAC vs CP 0.78 0.22 0.30 0.32 0.24 0.46 0.34 0.36 0.44 0.36 0.23 23 PDAC vs CP 0.77 0.23 0.29 0.34 0.26 0.45 0.30 0.31 0.35 0.37 0.22 24 PDAC vs CP 0.81 0.25 0.30 0.30 0.24 0.33 0.26 0.23 0.31 0.28 0.20 25 PDAC vs CP 0.79 0.24 0.29 0.31 0.25 0.43 0.31 0.33 0.40 0.35 0.20 26 PDAC vs CP 0.78 0.22 0.30 0.32 0.26 0.43 0.36 0.34 0.46 0.33 0.25 27 PDAC vs CP 0.76 0.23 0.30 0.34 0.26 0.40 0.33 0.29 0.37 0.34 0.26 28 PDAC vs CP 0.78 0.24 0.31 0.31 0.25 0.30 0.28 0.24 0.33 0.27 0.22 29 PDAC vs CP 0.79 0.24 0.28 0.32 0.25 0.41 0.33 0.32 0.41 0.32 0.21 30 PDAC vs CP 0.77 0.22 0.25 0.27 0.20 0.54 0.35 0.36 0.44 0.39 0.21 31 PDAC vs CP 0.81 0.23 0.28 0.25 0.20 0.36 0.28 0.22 0.27 0.29 0.19 32 PDAC vs CP 0.76 0.23 0.27 0.26 0.21 0.55 0.33 0.33 0.40 0.39 0.17 33 PDAC vs CP 0.79 0.21 0.27 0.27 0.24 0.46 0.33 0.31 0.33 0.42 0.18 34 PDAC vs CP 0.79 0.23 0.25 0.28 0.24 0.49 0.39 0.35 0.46 0.37 0.22 35 PDAC vs CP 0.77 0.24 0.26 0.28 0.24 0.45 0.37 0.30 0.35 0.40 0.21 36 PDAC vs CP 0.80 0.23 0.28 0.25 0.22 0.32 0.31 0.22 0.30 0.28 0.20 37 PDAC vs CP 0.77 0.23 0.27 0.29 0.24 0.54 0.36 0.33 0.42 0.36 0.18 38 PDAC vs CP 0.78 0.22 0.27 0.27 0.23 0.36 0.18 0.27 0.24 0.30 0.11 39 PDAC vs CP 0.81 0.23 0.28 0.26 0.26 0.28 0.16 0.20 0.21 0.24 0.13 40 PDAC vs CP 0.79 0.22 0.26 0.26 0.23 0.39 0.19 0.28 0.29 0.30 0.11 41 PDAC vs CP 0.80 0.20 0.26 0.34 0.29 0.41 0.31 0.33 0.25 0.36 0.17 42 PDAC vs CP 0.82 0.21 0.26 0.30 0.32 0.28 0.27 0.23 0.21 0.30 0.17 43 PDAC vs CP 0.78 0.19 0.30 0.24 0.22 0.41 0.30 0.29 0.27 0.29 0.12 44 PDAC vs CP 0.80 0.21 0.30 0.22 0.21 0.33 0.26 0.24 0.24 0.24 0.12 45 PDAC vs CP 0.78 0.20 0.27 0.33 0.28 0.42 0.30 0.31 0.29 0.35 0.16 46 PDAC vs CP 0.78 0.20 0.28 0.21 0.22 0.42 0.29 0.33 0.31 0.30 0.11 47 PDAC vs CP 0.79 0.21 0.28 0.25 0.22 0.42 0.33 0.28 0.29 0.25 0.18 48 PDAC vs CP 0.78 0.22 0.28 0.25 0.22 0.34 0.29 0.24 0.25 0.20 0.17 49 PDAC vs CP 0.78 0.22 0.27 0.24 0.22 0.45 0.32 0.31 0.33 0.26 0.15 50 PDAC vs CP 0.78 0.21 0.26 0.37 0.31 0.39 0.34 0.31 0.25 0.35 0.20 51 PDAC vs CP 0.81 0.23 0.27 0.34 0.32 0.30 0.29 0.23 0.21 0.28 0.19 52 PDAC vs CP 0.79 0.23 0.25 0.33 0.32 0.44 0.33 0.32 0.30 0.34 0.16 53 PDAC vs CP 0.78 0.22 0.26 0.30 0.26 0.34 0.20 0.26 0.26 0.28 0.16 54 PDAC vs CP 0.79 0.25 0.26 0.27 0.25 0.29 0.17 0.21 0.22 0.22 0.14 55 PDAC vs CP 0.77 0.25 0.26 0.29 0.25 0.37 0.21 0.28 0.30 0.29 0.13 56 PDAC vs CP 0.77 0.18 0.27 0.39 0.31 0.44 0.34 0.35 0.39 0.40 0.25 57 PDAC vs CP 0.80 0.20 0.28 0.31 0.25 0.40 0.20 0.29 0.39 0.34 0.18 58 PDAC vs CP 0.81 0.19 0.28 0.28 0.24 0.39 0.34 0.36 0.44 0.37 0.19 59 PDAC vs CP 0.78 0.20 0.26 0.40 0.32 0.43 0.31 0.31 0.29 0.37 0.24 60 PDAC vs CP 0.81 0.23 0.29 0.38 0.32 0.30 0.27 0.22 0.26 0.29 0.23 61 PDAC vs CP 0.81 0.20 0.28 0.30 0.26 0.39 0.17 0.25 0.30 0.30 0.16 62 PDAC vs CP 0.80 0.23 0.29 0.29 0.26 0.27 0.15 0.19 0.26 0.23 0.16 63 PDAC vs CP 0.78 0.21 0.28 0.37 0.31 0.42 0.31 0.32 0.35 0.39 0.21 64 PDAC vs CP 0.79 0.22 0.30 0.30 0.25 0.40 0.19 0.29 0.35 0.33 0.16 65 PDAC vs CP 0.79 0.19 0.30 0.30 0.24 0.35 0.30 0.31 0.35 0.35 0.17 66 PDAC vs CP 0.80 0.21 0.32 0.26 0.26 0.27 0.26 0.26 0.31 0.28 0.15 67 PDAC vs CP 0.79 0.19 0.31 0.27 0.25 0.38 0.30 0.33 0.39 0.33 0.15 68 PDAC vs CP 0.78 0.18 0.27 0.41 0.34 0.41 0.37 0.35 0.40 0.39 0.27 69 PDAC vs CP 0.80 0.23 0.28 0.32 0.25 0.39 0.21 0.28 0.40 0.32 0.18 70 PDAC vs CP 0.82 0.21 0.26 0.29 0.26 0.39 0.37 0.34 0.46 0.34 0.26 71 PDAC vs CP 0.81 0.22 0.29 0.29 0.25 0.39 0.33 0.32 0.41 0.33 0.22 72 PDAC vs CP 0.79 0.21 0.24 0.43 0.34 0.41 0.34 0.31 0.30 0.35 0.28 73 PDAC vs CP 0.80 0.23 0.28 0.39 0.33 0.28 0.28 0.22 0.26 0.28 0.25 74 PDAC vs CP 0.77 0.23 0.28 0.40 0.33 0.39 0.34 0.33 0.35 0.38 0.23 75 PDAC vs CP 0.81 0.23 0.28 0.32 0.25 0.36 0.19 0.24 0.31 0.29 0.19 76 PDAC vs CP 0.79 0.26 0.29 0.31 0.27 0.25 0.16 0.19 0.27 0.21 0.18 77 PDAC vs CP 0.79 0.25 0.29 0.32 0.27 0.41 0.20 0.29 0.36 0.32 0.17 78 PDAC vs CP 0.81 0.22 0.28 0.29 0.25 0.36 0.34 0.29 0.37 0.32 0.23 79 PDAC vs CP 0.79 0.22 0.31 0.28 0.27 0.27 0.29 0.24 0.33 0.25 0.23 80 PDAC vs CP 0.78 0.19 0.26 0.33 0.26 0.51 0.36 0.37 0.39 0.41 0.24 81 PDAC vs CP 0.80 0.20 0.26 0.27 0.21 0.49 0.21 0.29 0.39 0.34 0.16 82 PDAC vs CP 0.80 0.18 0.26 0.24 0.21 0.54 0.37 0.38 0.45 0.40 0.17 83 PDAC vs CP 0.81 0.22 0.28 0.32 0.27 0.35 0.29 0.20 0.23 0.30 0.23 84 PDAC vs CP 0.79 0.21 0.26 0.33 0.28 0.53 0.34 0.34 0.35 0.43 0.20 85 PDAC vs CP 0.79 0.22 0.26 0.27 0.24 0.47 0.18 0.25 0.28 0.32 0.14 86 PDAC vs CP 0.81 0.21 0.29 0.25 0.23 0.32 0.15 0.17 0.23 0.25 0.15 87 PDAC vs CP 0.78 0.21 0.28 0.27 0.22 0.49 0.20 0.27 0.35 0.35 0.15 88 PDAC vs CP 0.77 0.21 0.28 0.28 0.23 0.49 0.35 0.31 0.34 0.38 0.15 89 PDAC vs CP 0.77 0.21 0.30 0.23 0.22 0.38 0.30 0.25 0.29 0.30 0.14 90 PDAC vs CP 0.79 0.21 0.30 0.27 0.22 0.57 0.33 0.34 0.39 0.39 0.13 91 PDAC vs CP 0.79 0.20 0.24 0.34 0.30 0.46 0.35 0.32 0.28 0.42 0.22 92 PDAC vs CP 0.79 0.21 0.26 0.29 0.26 0.52 0.42 0.35 0.47 0.37 0.24 93 PDAC vs CP 0.80 0.17 0.25 0.37 0.31 0.52 0.40 0.37 0.39 0.41 0.26 94 PDAC vs CP 0.80 0.21 0.25 0.27 0.24 0.47 0.22 0.29 0.40 0.33 0.16 95 PDAC vs CP 0.77 0.21 0.26 0.29 0.25 0.49 0.39 0.30 0.36 0.37 0.22 96 PDAC vs CP 0.78 0.23 0.30 0.26 0.24 0.40 0.33 0.25 0.31 0.29 0.22 97 PDAC vs CP 0.77 0.22 0.28 0.27 0.24 0.53 0.38 0.34 0.42 0.36 0.19 98 PDAC vs CP 0.80 0.19 0.24 0.38 0.32 0.46 0.39 0.34 0.28 0.39 0.27 99 PDAC vs CP 0.81 0.20 0.27 0.33 0.30 0.37 0.32 0.21 0.23 0.27 0.25 100 PDAC vs CP 0.77 0.21 0.25 0.36 0.31 0.55 0.38 0.33 0.35 0.42 0.23 101 PDAC vs CP 0.79 0.23 0.26 0.29 0.26 0.46 0.20 0.24 0.29 0.30 0.17 102 PDAC vs CP 0.79 0.23 0.29 0.27 0.23 0.33 0.17 0.17 0.25 0.23 0.16 103 PDAC vs CP 0.77 0.23 0.28 0.30 0.24 0.46 0.22 0.28 0.36 0.33 0.15 104 PDAC vs CP 0.79 0.15 0.26 0.31 0.29 0.38 0.32 0.31 0.31 0.32 0.18 105 PDAC vs CP 0.79 0.19 0.29 0.14 0.13 0.32 0.24 0.27 0.23 0.27 0.20 with two-model algorithm according to CA19-9 level 106 PDAC vs CP 0.80 0.17 0.30 0.16 0.14 0.29 0.18 0.30 0.24 0.29 0.18 with two-model algorithm according to CA19-9 level 105 PDAC vs CP 0.79 0.17 0.24 0.21 0.17 0.32 0.24 0.21 0.23 0.24 0.14 with same model for all samples 106 PDAC vs CP 0.79 0.16 0.21 0.21 0.18 0.29 0.18 0.18 0.24 0.19 0.14 with same model for all samples Panel Median of prediction score for group number No. 12 13 14 15 16 17 18 19 20 21 22 3 1 0.24 0.12 0.18 0.18 0.15 0.18 0.20 0.16 0.16 0.16 0.22 3 2 0.23 0.10 0.18 0.16 0.15 0.14 0.20 0.18 0.15 0.11 0.20 0.24 3 0.21 0.11 0.16 0.16 0.14 0.15 0.17 0.14 0.15 0.13 0.20 0.22 4 0.25 0.14 0.18 0.20 0.18 0.22 0.22 0.19 0.19 0.17 0.26 0.31 5 0.21 0.11 0.16 0.16 0.14 0.15 0.17 0.14 0.15 0.13 0.20 0.22 6 0.20 0.11 0.16 0.15 0.14 0.15 0.17 0.14 0.15 0.12 0.20 0.23 7 0.19 0.10 0.15 0.15 0.12 0.14 0.18 0.14 0.13 0.13 0.19 0.26 8 0.19 0.09 0.15 0.14 0.12 0.14 0.16 0.12 0.13 0.11 0.18 0.23 9 0.19 0.09 0.17 0.12 0.13 0.12 0.18 0.14 0.14 0.10 0.18 0.20 10 0.19 0.09 0.16 0.12 0.13 0.11 0.18 0.14 0.13 0.09 0.18 0.20 11 0.22 0.10 0.17 0.14 0.18 0.15 0.22 0.19 0.16 0.11 0.21 0.23 12 0.29 0.15 0.23 0.21 0.18 0.20 0.23 0.19 0.20 0.21 0.26 0.29 13 0.25 0.14 0.22 0.18 0.17 0.16 0.23 0.20 0.17 0.14 0.20 0.28 14 0.31 0.17 0.22 0.23 0.22 0.23 0.24 0.22 0.22 0.20 0.29 0.32 15 0.27 0.14 0.19 0.19 0.18 0.17 0.20 0.16 0.18 0.15 0.22 0.26 16 0.24 0.13 0.22 0.21 0.16 0.20 0.21 0.19 0.16 0.17 0.23 0.31 17 0.22 0.13 0.19 0.18 0.15 0.18 0.21 0.17 0.17 0.16 0.23 0.24 18 0.18 0.12 0.16 0.16 0.13 0.14 0.17 0.15 0.14 0.12 0.20 0.25 19 0.28 0.16 0.25 0.22 0.18 0.21 0.24 0.21 0.20 0.21 0.29 0.29 20 0.26 0.17 0.24 0.21 0.18 0.19 0.23 0.21 0.19 0.20 0.25 0.29 21 0.23 0.15 0.19 0.18 0.16 0.16 0.20 0.17 0.17 0.16 0.23 0.24 22 0.27 0.18 0.25 0.25 0.21 0.25 0.27 0.23 0.21 0.18 0.27 1 23 0.26 0.18 0.24 0.25 0.21 0.24 0.26 0.20 0.21 0.17 0.28 9 24 0.25 0.19 0.24 0.23 0.19 0.23 0.26 0.21 0.18 0.16 0.27 7 25 0.23 0.17 0.21 0.22 0.18 0.23 0.24 0.20 0.17 0.14 0.25 6 26 0.31 0.21 0.28 0.27 0.24 0.27 0.29 0.23 0.24 0.20 0.30 4 27 0.31 0.21 0.31 0.28 0.25 0.26 0.30 0.24 0.24 0.21 0.31 5 28 0.29 0.21 0.27 0.26 0.24 0.25 0.29 0.24 0.23 0.21 0.29 1 29 0.27 0.20 0.24 0.24 0.21 0.24 0.26 0.22 0.21 0.17 0.26 0.29 30 0.21 0.14 0.21 0.21 0.17 0.19 0.24 0.19 0.19 0.14 0.25 3 31 0.22 0.15 0.22 0.20 0.16 0.20 0.21 0.19 0.17 0.13 0.24 2 32 0.20 0.14 0.18 0.19 0.15 0.18 0.21 0.17 0.15 0.13 0.22 2 33 0.21 0.16 0.22 0.24 0.18 0.20 0.22 0.20 0.20 0.14 0.27 5 34 0.24 0.18 0.25 0.24 0.19 0.21 0.26 0.22 0.22 0.16 0.25 2 35 0.26 0.19 0.29 0.28 0.21 0.21 0.28 0.22 0.22 0.18 0.29 1 36 0.25 0.19 0.27 0.23 0.20 0.21 0.26 0.21 0.21 0.18 0.28 0.31 37 0.23 0.17 0.22 0.22 0.18 0.20 0.24 0.19 0.20 0.15 0.25 0.27 38 0.21 0.11 0.19 0.17 0.15 0.15 0.18 0.15 0.15 0.12 0.22 0.28 39 0.21 0.12 0.17 0.16 0.17 0.17 0.19 0.17 0.15 0.13 0.21 0.21 40 0.19 0.11 0.15 0.13 0.13 0.15 0.16 0.14 0.13 0.11 0.18 0.21 41 0.26 0.16 0.23 0.23 0.20 0.23 0.24 0.20 0.19 0.17 0.28 0.33 42 0.25 0.15 0.20 0.19 0.20 0.21 0.22 0.20 0.18 0.19 0.26 0.27 43 0.20 0.10 0.19 0.16 0.14 0.15 0.18 0.19 0.14 0.10 0.20 0.23 44 0.19 0.11 0.18 0.15 0.14 0.14 0.19 0.18 0.14 0.10 0.18 0.21 45 0.22 0.13 0.14 0.17 0.16 0.17 0.19 0.17 0.15 0.15 0.23 0.28 46 0.17 0.09 0.16 0.13 0.11 0.13 0.17 0.15 0.12 0.08 0.17 0.20 47 0.24 0.12 0.22 0.19 0.17 0.16 0.21 0.22 0.16 0.12 0.23 0.27 48 0.24 0.13 0.19 0.17 0.16 0.16 0.21 0.20 0.16 0.13 0.20 0.28 49 0.21 0.11 0.18 0.15 0.12 0.15 0.19 0.17 0.14 0.11 0.18 0.24 50 0.31 0.18 0.27 0.25 0.25 0.24 0.27 0.24 0.23 0.21 0.33 0.35 51 0.29 0.18 0.22 0.22 0.22 0.24 0.27 0.23 0.20 0.22 0.30 0.32 52 0.28 0.16 0.17 0.19 0.20 0.19 0.20 0.19 0.17 0.18 0.26 0.28 53 0.27 0.13 0.22 0.20 0.18 0.17 0.21 0.17 0.18 0.16 0.26 0.28 54 0.25 0.14 0.20 0.17 0.19 0.17 0.21 0.19 0.18 0.16 0.23 0.25 55 0.23 0.13 0.18 0.16 0.17 0.16 0.19 0.17 0.16 0.15 0.21 3 56 0.30 0.16 0.22 0.24 0.25 0.24 0.27 0.21 0.23 0.19 0.30 2 57 0.26 0.14 0.20 0.18 0.18 0.18 0.23 0.16 0.19 0.14 0.24 3 58 0.25 0.15 0.23 0.19 0.20 0.20 0.26 0.23 0.20 0.14 0.23 59 0.28 0.19 0.23 0.26 0.26 0.25 0.27 0.21 0.22 0.20 0.33 60 0.30 0.19 0.19 0.23 0.23 0.24 0.27 0.22 0.21 0.19 0.30 61 0.25 0.14 0.22 0.18 0.19 0.16 0.22 0.16 0.17 0.14 0.25 6 62 0.24 0.15 0.21 0.18 0.19 0.17 0.23 0.18 0.18 0.14 0.21 0.21 63 0.26 0.17 0.18 0.20 0.19 0.24 0.23 0.20 0.17 0.15 0.26 0.27 64 0.22 0.13 0.18 0.16 0.18 0.16 0.20 0.16 0.16 0.12 0.19 1 65 0.24 0.14 0.24 0.20 0.19 0.20 0.24 0.20 0.21 0.11 0.23 5 66 0.22 0.15 0.21 0.19 0.19 0.18 0.25 0.21 0.18 0.12 0.25 6 67 0.20 0.13 0.19 0.15 0.15 0.16 0.23 0.18 0.16 0.11 0.20 2 68 0.35 0.20 0.26 0.27 0.31 0.26 0.31 0.23 0.27 0.22 0.32 5 69 0.31 0.16 0.23 0.21 0.21 0.19 0.25 0.19 0.21 0.17 0.26 7 70 0.28 0.17 0.25 0.23 0.21 0.21 0.30 0.25 0.21 0.17 0.24 0.30 71 0.25 0.15 0.23 0.20 0.19 0.18 0.27 0.21 0.21 0.14 0.23 0.28 72 0.33 0.23 0.28 0.29 0.30 0.27 0.32 0.24 0.26 0.24 0.36 0.38 73 0.32 0.22 0.25 0.26 0.27 0.26 0.32 0.24 0.25 0.22 0.34 0.32 74 0.30 0.19 0.21 0.23 0.24 0.26 0.27 0.21 0.22 0.19 0.29 0.31 75 0.30 0.16 0.24 0.20 0.23 0.17 0.25 0.20 0.22 0.17 0.29 0.30 76 0.28 0.16 0.21 0.20 0.23 0.18 0.25 0.19 0.21 0.16 0.23 0.25 77 0.25 0.15 0.20 0.19 0.21 0.17 0.23 0.18 0.19 0.15 0.23 0.25 78 0.27 0.17 0.29 0.23 0.20 0.22 0.27 0.23 0.25 0.15 0.27 0.31 79 0.29 0.16 0.25 0.23 0.23 0.20 0.30 0.24 0.24 0.16 0.26 0.30 80 0.24 0.14 0.19 0.21 0.19 0.19 0.24 0.20 0.20 0.16 0.28 0.28 81 0.22 0.12 0.18 0.16 0.14 0.15 0.19 0.14 0.17 0.12 0.22 0.23 82 0.21 0.13 0.20 0.18 0.18 0.16 0.23 0.18 0.19 0.11 0.22 0.21 83 0.25 0.17 0.19 0.22 0.19 0.21 0.24 0.21 0.19 0.17 0.29 0.25 84 0.23 0.15 0.17 0.19 0.19 0.20 0.22 0.18 0.17 0.14 0.24 0.23 85 0.20 0.12 0.20 0.18 0.16 0.14 0.19 0.15 0.17 0.12 0.22 0.23 86 0.20 0.13 0.17 0.16 0.15 0.14 0.20 0.15 0.15 0.12 0.21 0.20 87 0.20 0.13 0.16 0.16 0.17 0.15 0.19 0.15 0.14 0.11 0.20 0.21 88 0.24 0.13 0.23 0.20 0.18 0.18 0.22 0.21 0.19 0.11 0.22 0.21 89 0.22 0.13 0.22 0.20 0.18 0.15 0.22 0.21 0.18 0.10 0.23 9 90 0.19 0.12 0.17 0.15 0.15 0.14 0.19 0.17 0.15 0.09 0.20 6 91 0.24 0.17 0.24 0.24 0.23 0.22 0.25 0.22 0.20 0.17 0.31 8 92 0.24 0.16 0.25 0.21 0.18 0.19 0.28 0.23 0.23 0.15 0.25 4 93 0.31 0.19 0.24 0.25 0.24 0.21 0.26 0.23 0.24 0.18 0.29 7 94 0.25 0.13 0.20 0.19 0.18 0.18 0.21 0.16 0.20 0.14 0.24 7 95 0.28 0.16 0.29 0.22 0.19 0.18 0.25 0.25 0.22 0.14 0.26 9 96 0.25 0.16 0.26 0.21 0.22 0.18 0.25 0.23 0.22 0.14 0.25 0.23 97 0.23 0.15 0.23 0.18 0.18 0.16 0.23 0.21 0.19 0.11 0.23 0.20 98 0.30 0.21 0.25 0.29 0.27 0.23 0.29 0.24 0.24 0.21 0.37 6 99 0.28 0.20 0.25 0.24 0.22 0.24 0.28 0.24 0.23 0.21 0.31 2 100 0.27 0.17 0.20 0.22 0.22 0.24 0.24 0.21 0.21 0.19 0.28 1 101 0.24 0.14 0.24 0.20 0.20 0.15 0.21 0.16 0.19 0.15 0.25 7 102 0.25 0.16 0.23 0.18 0.20 0.15 0.23 0.19 0.19 0.15 0.24 5 103 0.23 0.14 0.20 0.18 0.18 0.15 0.18 0.17 0.17 0.13 0.20 6 104 0.22 0.11 0.19 0.16 0.19 0.16 0.24 0.20 0.16 0.12 0.23 0.25 105 0.20 0.13 0.21 0.17 0.17 0.18 0.21 0.18 0.20 0.13 0.18 0.24 106 0.19 0.10 0.17 0.13 0.16 0.13 0.20 0.20 0.18 0.10 0.17 0.19 105 0.18 0.11 0.17 0.15 0.13 0.13 0.19 0.15 0.15 0.12 0.18 0.24 106 0.17 0.10 0.16 0.12 0.13 0.11 0.16 0.14 0.13 0.09 0.17 0.19 indicates data missing or illegible when filed