Lipidomic analysis of bile from patients with extrahepatic cholangiocarcinoma

Abstract

Objective Cholangiocarcinoma and gallstones are significant gastrointestinal diseases with diverse etiologies and complex clinical manifestations. Understanding their underlying molecular mechanisms is crucial for advancing diagnosis and treatment strategies. In this study, we compared the lipidomic profiles of bile samples from patients with extrahepatic cholangiocarcinoma (eCCA) or choledocholithiasis with those of healthy controls to identify potential biomarkers and therapeutic targets. Methods Bile samples were prospectively collected from 33 patients undergoing endoscopic retrograde cholangiopancreatography at the Korea University Guro Hospital, including 12 patients with eCCA, 15 with choledocholithiasis, and six controls. Lipidomic profiling was performed using ultra-high-performance liquid chromatography coupled with tandem mass spectrometry. Principal component analysis, ANOVA, and volcano plots were used to identify the differential lipidomic signatures across the groups. Results A total of 230 lipid metabolites were identified, and significant differences were observed among the groups; each group had distinct lipidomic patterns. In both eCCA and choledocholithiasis, phosphatidylcholine contents were consistently more downregulated than in controls. However, diacylglycerol lipids were upregulated in eCCA while acylcarnitine lipids were upregulated in choledocholithiasis. Lysophosphatidylcholine levels were notably lower in patients with eCCA than in those with choledocholithiasis. Conclusion Our results suggested that specific lipidomic changes and their inter-relationships contribute to the pathophysiology of choledocholithiasis and eCCA. Longitudinal studies and functional assays can further validate the findings and translate them into clinical practice.