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

ABSTRACT: 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 was 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 was 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 range, recovery of 89% to 104%, and intra-assay and interassay precision of 10.2% to 19.6% and 13.7% to 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 modeling 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 vs. AUCCA19-9 = 0.81 or AUCMIA = 0.75 only, P < 0.05) or IPMN (AUCCA19-9+MIC-1 = 0.81 vs. AUCCA19-9 = 0.75 or AUCMIC-1 = 0.73 only, P < 0.05). It was observed that osteopontin (OPN) outperformed CA19-9 in separating IPMN from chronic pancreatitis (AUCOPN = 0.80 vs. 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.

SUBMITTER: Song J 

PROVIDER: S-EPMC6324978 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature