Discovery and Qualification of Serum Protein Biomarker Candidates for Cholangiocarcinoma Diagnosis

Cholangiocarcinoma (CCA) is a major health problem in northeastern Thailand. The majority of CCA cases are clinically silent and difficult to detect at an early stage. Although abdominal ultrasonography (US) can detect pre-malignant periductal fibrosis (PDF), this method is not suitable for screening populations in remote areas. With the goal of developing a blood test for detecting CCA in the at-risk population, we carried out serum protein biomarker discovery and qualification. Label-free shotgun proteomics was performed on depleted serum samples from 30 participants (n=10 for US-normal, US-PDF and CCA groups). Of 42 protein candidates selected using multiple reactions monitoring on 90 additional serum samples (n=30 per group), 11 discriminatory proteins were obtained using supervised multivariate statistical analysis. We further evaluated 3 candidates using ELISA and immunohistochemistry (IHC). S100A9, thioredoxin (TRX) and cadherin-related family member 2 (CDHR2) were significantly different between C...