MALDI-TOF/MS biomarkers discovery for pancreatic cancer diagnosis: emerging role of apolipoprotein A1 and complement C3

Introduction: New serum biomarkers are needed for pancreatic cancer (PCa) diagnosis especially among patients with diabetes mellitus (DM ), a risk factor for and a consequence of PCa. Aim: to validate new serum biomarkers identified by MALDI -TOF /MS for PCa diagnosis. Patients and methods: MALDI -TOF /MS analysis was performed in sera from 22 controls, 51 PCa, 37 chronic pancreatitis (ChrPa), 24 DM , 29 gastric cancer (GC), 24 chronic gastritis (CG). Results: 11/160 selected features (m/z range 1200-5000) were highly correlated with pancreatic diseases (univariate and binary recursive partitioning tree analyses). By MALDI - TOF -TOF analysis three features (1530, 1550, 1778 m/z) were found to be part of clusterin, human apolipoprotein A1 (Apo-A1), human complement C3. Apo-A1 and C3 were measured in 172/187 sera and in an additional series of 69 new samples yielding 30 controls, 81 PCa, 26 ChrPa, 51 DM , 32 GC, 21 CG. Apo-A1 was reduced in PCa and in GC (F=10.49, p<0.0001). In 22/81 (27.2%) PCa and in 2/32 (6.2%) GC Apo-A1 values were below 0.6 g/L, while values in this order of magnitude were never found in the other groups (100% specificity). Apo-A1, C3 and CA 19-9 were correlated with PCa diagnosis at univariate logistic regression analysis; at multivariate logistic regression only Apo-A1 (OR=0.38, 95% CI=0.17-0.86, p=0.020) and C3 (OR=4.75, 95% CI=2.33-9.67, p<0.001) were confirmed to be strictly correlated with PCa. Conclusion: reduced serum levels of the anti-inflammatory and antioxidant protein Apo-A1, major protein in HDL , and increased serum levels of the inflammatory mediator C3 are potential biomarkers for PCa.