Differential plasma proteomes of the patients with Opisthorchiasis viverrini and cholangiocarcinoma identify a polymeric immunoglobulin receptor as a potential biomarker

Abstract

In Southeast Asian countries, nitrosamine compounds and the liver fluke Opisthorchis viverrini have long been identified as carcinogens for cholangiocarcinoma (CHCA). In order to effectively treat O. viverrini infections and prevent the development of CHCA, methods for disease detection are needed. This study aims to identify biomarkers for O. viverrini infection and CHCA. In the discovery phase, technical triplicates of five pooled plasma pools (10 plasma each) of healthy control subjects (noOVCCA), O. viverrini subjects (OV), and cholangiocarcinoma subjects (CCA), underwent solution-based digestion, with the label-free method, using a Thermo Scientific™ Q Exactive™ HF hybrid quadrupole-Orbitrap mass spectrometer and UltiMate 300 LC systems. The noOVCCA, OV, and CCA groups demonstrated different profiles and were clustered, as illustrated by PCA and heat map analysis. The STRING and reactome analysis showed that both OV and CCA groups up-regulated proteins targeting immune system-related proteins. Differential proteomic profiles, S100A9, and polymeric immunoglobulin receptor (PIGR) were specifically expressed in the CCA group. During the validation phase, another 50 plasma samples were validated via the PIGR sandwich ELISA. Using PIGR >1.559 ng/ml as a cut-off point, 78.00% sensitivity, 71.00% specificity, and AUC = 0.8216, were obtained. It is sufficient to differentially diagnose cholangiocarcinoma patients from healthy patients and those with Opisthorchiasis viverrini. Hence, in this study, PIGR was identified and validated as a potential biomarker for CHCA. Plasma PIGR is suggested for screening CHCA, especially in an endemic region of O. viverrini infection.

Keywords

• Plasma proteome
• LC-MS/MS
• Cholangiocarcinoma
• Opisthorchis viverrini
• S100A9
• PIGR