Biomarker Development for Intraductal Papillary Mucinous Neoplasms Using Multiple Reaction Monitoring Mass Spectrometry

Intraductal
papillary mucinous neoplasm (IPMN) is a common precursor
of pancreatic cancer (PC). Much clinical attention has been directed
toward IPMNs due to the increase in the prevalence of PC. The diagnosis
of IPMN depends primarily on a radiological examination, but the diagnostic
accuracy of this tool is not satisfactory, necessitating the development
of accurate diagnostic biomarkers for IPMN to prevent PC. Recently,
high-throughput targeted proteomic quantification methods have accelerated
the discovery of biomarkers, rendering them powerful platforms for
the evolution of IPMN diagnostic biomarkers. In this study, a robust
multiple reaction monitoring (MRM) pipeline was applied to discovery
and verify IPMN biomarker candidates in a large cohort of plasma samples.
Through highly reproducible MRM assays and a stringent statistical
analysis, 11 proteins were selected as IPMN marker candidates with
high confidence in 184 plasma samples, comprising a training (n = 84) and test set (n = 100). To improve
the discriminatory power, we constructed a six-protein panel by combining
marker candidates. The multimarker panel had high discriminatory power
in distinguishing between IPMN and controls, including other benign
diseases. Consequently, the diagnostic accuracy of IPMN can be improved
dramatically with this novel plasma-based panel in combination with
a radiological examination.