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

胆管细胞癌(CC)通常诊断为晚期，预后较差。蛋白质组学分析可能有助于识别早期检测、预防和治疗CC的新生物标志物。本研究的目的是鉴定CC中差异过表达的蛋白质，并验证这些蛋白质是否为潜在的生物标记物。我们用鸟枪式LC-MS/MS对福尔马林固定的石蜡包埋(FEPE)组织进行了全程蛋白质组学研究，共鉴定出约2000个蛋白质，统计比较表明，与非癌胆管相比，癌组织中有160个蛋白质过表达。我们应用了一种基于选择性反应监测(SRM)的靶向蛋白质组学方法来量化这些蛋白质的子集。SRM分析表明，一些蛋白质可能是有用的潜在生物标志物。免疫组织化学方法证实这些蛋白的表达。使用大规模FFPE组织样本集的进一步验证目前正在进行中。

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.