Early Detection Research Network

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

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.

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; <i>n</i> = 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.

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<sub>CA19-9+MIA</sub> = 0.86 vs. AUC<sub>CA19-9</sub> = 0.81 or AUC<sub>MIA</sub> = 0.75 only, <i>P</i> < 0.05) or IPMN (AUC<sub>CA19-9+MIC-1</sub> = 0.81 vs. AUC<sub>CA19-9</sub> = 0.75 or AUC<sub>MIC-1</sub> = 0.73 only, <i>P</i> < 0.05). It was observed that osteopontin (OPN) outperformed CA19-9 in separating IPMN from chronic pancreatitis (AUC<sub>OPN</sub> = 0.80 vs. AUC<sub>CA19-9</sub> = 0.70, <i>P</i> < 0.01).

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.

The validated biomarker panels could lead to earlier intervention and better outcomes.

Bach DM, Chan DW, Li H, Pasay JJ, Rubin AL, Sokoll LJ, Song J, Zhang Z

30333219

Cancer Epidemiol. Biomarkers Prev., 2019, 28 (1)

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