4.5 Article

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

Journal

CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
Volume 28, Issue 1, Pages 174-182

Publisher

AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1055-9965.EPI-18-0483

Keywords

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Funding

  1. NIH/NCI Early Detection Research Network [U24 CA115102, U01 CA200469]

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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 (AUC(CA19-9+MIA) = 0.86 vs. AUC(CA19-9) = 0.81 or AUC(MIA) = 0.75 only, P < 0.05) or IPMN (AUC(CA19-9+MIC-1) = 0.81 vs. AUC(CA19-9) = 0.75 or AUC(MIC-1) = 0.73 only, P < 0.05). It was observed that osteopontin (OPN) outperformed CA19-9 in separating IPMN from chronic pancreatitis (AUC(OPN) = 0.80 vs. AUC(CA19-9) = 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.

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