A Proteomics and Metabolomics-based Approach to Biomarkers Identification for the Early Diagnosis of Cholangiocarcinoma in a Hamster Model: A Preliminary Study.

Abstract

BACKGROUND: Cholangiocarcinoma (CCA) poses a significant public health challenge, particularly in northeastern Thailand, where its prevalence is the highest worldwide. Early detection and effective treatment remain challenging due to the absence of sensitive and specific biomarkers. This study aimed to identify novel plasma proteins and metabolites as potential biomarkers for the early diagnosis of CCA. METHODS: Plasma samples from hamsters with Opisthorchis viverrini (OV)/dimethylnitrosamine (DMN)-induced CCA and healthy controls (n=3 per group) were analyzed by LC-MS/MS-based proteomics and metabolomics. RESULTS: More than 5,000 proteins were identified, including 572 unique to CCA hamsters at week 12. At weeks 8 and 12, 412 and 545 proteins, respectively, were functionally linked to cell proliferation, signal transduction, and metabolic regulation. Metabolomic analysis revealed 273 metabolites, with 59-including cystathionine, putrescine, UDP-N-acetyl-glucosamine, and FMN, upregulated in the CCA group. CONCLUSION: This study provides preliminary insights into candidate biomarkers for the early detection of CCA. These findings are intended to generate hypotheses for future research. Larger studies, including human validation cohorts, are warranted to confirm their clinical applicability.