Verification of diagnostic biomarker candidates for biliary and pancreatic carcinoma by SRM MS-based Multiple Assay

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Cholangiocarcinoma (CC) is usually diagnosed in advanced stage and associated with a dismal prognosis. A proteomic analysis may help identify novel biomarkers for the eraly detection, prevention and treatment of CC. The purpose of this study was to identify proteins differentially overexpressed in CC and to validate these proteins as potential biomarkers. We conducted a retrospective global proteomic sthdy of formalin-fixed parafiin-embedded (FEPE) tissues by shotgun LC-MS/MS. We identified abouto 2000 proteins, and statistical comparison showed that 160 proteins were overexpressed in CC compared to noncancerous bile duct. We applied a targeted proteomics approach based on selected reaction monitoring (SRM) to quantify a subset of these proteins. SRM analysis suggested that some proteins would be useful as potential biomarkers. Expression of these proteins was cinfirmed by immunohistochemistry. Further validation using a large-scale sample set of FFPE tissues is now under way.