Identification of Serum Biomarker Panels for the Early Detection of Pancreatic Cancer.
Abstact
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.
Authors
- Bach DM
- Chan DW
- Li H
- Pasay JJ
- Rubin AL
- Sokoll LJ
- Song J
- Zhang Z