ORIGINAL RESEARCH article
Front. Med.
Sec. Gastroenterology
This article is part of the Research TopicResearch on Biomarkers for Immunotherapy in Gastrointestinal Tumors: Basic Exploration and Clinical ApplicationView all 8 articles
A Study on Bile from Patients with Recurrent Common Bile Duct Stones and Cholangiocarcinoma Following ERCP Using Non-Targeted Metabolomics
Provisionally accepted
- The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China
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Objective: This study aimed to investigate bile metabolic profiles in patients with common bile duct stones and cholangiocarcinoma using non-targeted LC–MS metabolomics, identify disease-associated metabolites and pathways, and develop metabolite-based models for predicting stone recurrence and facilitating CCA diagnosis. Methods: Bile samples and clinical data were collected from 50 patients undergoing ERCP with nasobiliary drainage at the Second Affiliated Hospital of Zhengzhou University (Jan–Jun 2025), including 20 primary choledocholithiasis (PDS), 15 recurrent choledocholithiasis (RDS), and 15 cholangiocarcinoma (CCA) cases. Small-molecule metabolites were profiled by LC–MS. PCA and OPLS-DA were performed, and differential metabolites were identified using criteria of P < 0.05, fold change <0.67 or >1.50, and VIP >1. Pathway enrichment analysis was conducted. Predictive models were constructed using selected metabolites and evaluated by ROC curves. Results: A total of 174 metabolites were identified, of which 32 were differentially expressed: 17 between PDS and RDS, 8 between PDS and CCA, and 7 between RDS and CCA. Significant enrichment was observed in unsaturated fatty acid, amino acid, and sphingolipid pathways. Four metabolites with consistent changes and AUC >0.7 were used to build a recurrence prediction model, achieving an AUC of 0.92, sensitivity of 86.7%, and specificity of 90.2%. In both stone and CCA groups, the combination of arachidonic acid and dimethyl phosphate outperformed traditional tumor markers (CA19-9 and CEA) in diagnostic performance. Conclusion: Patients with recurrent bile duct stones and cholangiocarcinoma exhibit distinct bile metabolic alterations. Specific bile metabolite combinations may serve as promising biomarkers for predicting stone recurrence and improving early diagnosis of cholangiocarcinoma.
Keywords: Bile, Cholangiocarcinoma, Common bile duct stones, non-targeted metabolomics, Recurrence
Received: 17 Dec 2025; Accepted: 10 Feb 2026.
Copyright: © 2026 kuang, lu, wu and wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: gaofeng lu
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