Identification of Serum Biomarker Panels for the Early Detection of Pancreatic Cancer

Background:Pancreatic cancer is a deadly disease for which available biomarkers, such as CA19-9, lack the desired sensitivity and specificity for early detection. Additional biomarkers are needed to improve both its sensitivity and specificity. Methods:Multiplex immunoassays were developed for selected biomarkers using a Bio-Plex 200 system and analytical performance optimized. All proteins were analyzed in sera of patients diagnosed with pancreatic ductal adenocarcinoma (PDAC, n=188) or benign pancreatic conditions (131), and healthy controls (89). The clinical performance of these markers were evaluated individually or in combination for their ability to complement CA19-9 for the early detection of pancreatic cancer. Results:A 6-plex immunoassay was developed with negligible cross-reactivity, wide dynamic ranges, recovery of 89-104%, and intra-assay and inter-assay precision of 10.2-19.6% and 13.7-29.3%, respectively. Individually, the best biomarkers to separate PDAC early stage from chronic pancreatitis or intraductal papillary mucinous neoplasm (IPMN) were CA19-9 and MIA or CA19-9 and MIC-1. Logistic regression modelling selected the two-marker panels that significantly improved the individual biomarker performance in discriminating PDAC early stage from chronic pancreatitis (AUCCA19-9+MIA=0.86 versus AUCCA19-9=0.81 or AUCMIA=0.75 only, p<0.05) or IPMN (AUCCA19-9+MIC-1=0.81 versus AUCCA19-9=0.75 or AUCMIC-1=0.73 only, p<0.05). It was observed that OPN outperformed CA19-9 in separating IPMN from chronic pancreatitis (AUCOPN=0.80 versus AUCCA19-9=0.70, p<0.01). Conclusions:The biomarker panels evaluated by assays with high analytical performance demonstrated potential complementary values to CA19-9, warranting additional clinical validation to determine their role in early detection of pancreatic cancer. Impact:The validated biomarker panels could lead to earlier intervention and better outcomes.