Identification of serum biomarker panels for the early detection of pancreatic cancer

Jin Song, Lori J. Sokoll, Jered J. Pasay, Abigail L. Rubin, Hanying Li, Dylan M. Bach, Daniel W. Chan, Zhen Zhang

Research output: Contribution to journalArticlepeer-review

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 (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.

Original languageEnglish (US)
Pages (from-to)174-182
Number of pages9
JournalCancer Epidemiology Biomarkers and Prevention
Volume28
Issue number1
DOIs
StatePublished - Jan 2019

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

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