Fig 1: Analysis of biomarkers in sera from PDAC patients, benign conditions, and healthy controls. (A–I), CA-125, HE4, KRT19, FOLR1, CEA, HGF, OPG, Tie-2, and CA19-9 in PDAC patients, benign conditions, and healthy controls are demonstrated in overlaid scatterplots and boxplots. Only serum levels of biomarkers demonstrating significant differences between CP, IPMN, and early stage PDAC, (or benign and PDAC) are asterisked (Mann–Whitney U test). Biomarker data were transformed prior to analysis (log-transformation followed by z-score). Bars indicate median value. *, p < 0.05; **, p < 0.01; ****, p < 0.0001.
Fig 2: Diagnostic performance of individual or combination of serum biomarkers in detection of early stage PDAC. Diagnostic performance of CA19-9, CA-125, HE4, KRT19, FOLR1, CEA, HGF, OPG, and Tie-2 as individual markers (A,C,E,G,I) and their complementary (B,D,F,H,J) in differentiating patients with benign versus healthy controls (A&B) or PDAC versus benign (C,D) or IPMN versus CP (E,F) or PDAC versus IPMN (G,H) or early stage PDAC versus IPMN (I,J). ROC curves with AUCs are presented along with their 95% CI in brackets. Logistic regression modeling was constructed including sex and age as cofactors and backward stepwise selected z-score transformed variables with the highest performance. The four-marker panel of HE4, Tie-2, OPG and HGF including age as a cofactor with an AUC = 0.881 (0.831–0.931) for benign versus healthy controls, the three-marker panel of CA19-9, CA-125 and HE4 including age as a cofactor with an AUC = 0.854 (0.806–0.901) for PDAC versus benign, the two-marker panel of HE4 and CEA including sex and age as cofactors with an AUC = 0.841 (0.767–0.915) for IPMN versus CP, the two-marker panel of CA19-9 and CA-125 with an AUC = 0.857 (0.803–0.911) for PDAC versus IPMN, and the two-marker panel of CA19-9 and CA-125 with an AUC = 0.805 (0.720–0.891) for early stage PDAC versus IPMN significantly improved the individual biomarker performance (p value: <0.0001, 0.0004, <0.0001, 0.0005, or 0.0113 for CA19-9; Delong test).
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