Quantitative proteomic analysis of bile in extrahepatic cholangiocarcinoma patients

Background and Aims: Extrahepatic cholangiocarcinoma (CCA) without liver-fluke is increasing. Multifactorial carcinogenesis makes it hard to find biomarkers related to CCA. Although there are a few studies of bile proteomics, these showed different protein profiles because of having heterogeneous groups of patients and different sampling methods. Our aim was to identify the specific bile proteins of extrahepatic CCA patients. Methods: We collected bile from 23 patients undergoing endoscopic nasobiliary drainage in Korea University Guro Hospital from May 2018 to January 2019. The CCA group included 18 patients diagnosed with extrahepatic CCA, and the control group included 5 patients with benign biliary conditions. We analyzed bile proteome using liquid chromatography mass spectrometry. We compared the relative abundance of various proteins in the CCA and control groups. Results: In all, we identified a total of 245 proteins in the bile of CCA and control patients. Increased top 14 proteins in CCA patients were immunoglobulin kappa light chain, apolipoprotein B, inter-alpha-trypsin inhibitor heavy chain H4, apolipoprotein E, Mucin 5B, inter-alpha-trypsin inhibitor heavy chain H1, apolipoprotein A-IV, intercellular adhesion molecule 1, complement C7, complement C5, apolipoprotein C-III, albumin, antithrombin-III, and apolipoprotein A-II. However, the significantly increased proteins in bile of CCA patients comparing with control patients were immunoglobulin kappa light chain, apolipoprotein E, albumin, apolipoprotein A-I, antithrombin-III, α1-antitrypsin, serotransferrin, immunoglobulin heavy constant mu, immunoglobulin J chain, complement C4-A, and complement C3 (p<0.05). Conclusions: In this study, we identified several proteins that were significantly increased in the bile of extrahepatic CCA. Further study is needed to validate them as potential tumor-associated proteins that may be potential biomarkers for CCA.