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Characterisation of the Serum Metabolic Signature of Cholangiocarcinoma in a United Kingdom Cohort

Lookup NU author(s): Professor Helen ReevesORCiD

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Abstract

© 2019 Indian National Association for Study of the Liver. Background: A distinct serum metabonomic pattern has been previously revealed to be associated with various forms of liver disease. Here, we aimed to apply mass spectrometry to obtain serum metabolomic profiles from individuals with cholangiocarcinoma and benign hepatobiliary diseases to gain an insight into pathogenesis and search for potential early-disease biomarkers. Methods: Serum samples were profiled using a hydrophilic interaction liquid chromatography platform, coupled to a mass spectrometer. A total of 47 serum specimens from 8 cholangiocarcinoma cases, 20 healthy controls, 8 benign disease controls (bile duct strictures) and 11 patients with hepatocellular carcinoma (as malignant disease controls) were included. Data analysis was performed using univariate and multivariate statistics. Results: The serum metabolome disparities between the metabolite profiles from healthy controls and patients with hepatobiliary disease were predominantly related to changes in lipid and lipid-derived compounds (phospholipids, bile acids and steroids) and amino acid metabolites (phenylalanine). A metabolic pattern indicative of inflammatory response due to cirrhosis and cholestasis was associated with the disease groups. The abundance of phospholipid metabolites was altered in individuals with liver disease, particularly cholangiocarcinoma, but no significant difference was seen between profiles from patients with benign biliary strictures and cholangiocarcinoma. Conclusion: The serum metabolome in cholangiocarcinoma exhibited changes in metabolites related to inflammation, altered energy production and phospholipid metabolism. This study serves to highlight future avenues for biomarker research in large-scale studies.

Publication metadata

Author(s): Alsaleh M, Leftley Z, Barbera TA, Koomson LK, Zabron A, Crossey MME, Reeves HL, Cramp M, Ryder S, Greer S, Prince M, Sithithaworn P, Shariff M, Khuntikeo N, Loilome W, Yongvanit P, Shen Y-L, Cox IJ, Williams R, Wadsworth CA, Holmes E, Nash K, Taylor-Robinson SD

Publication type: Article

Publication status: Published

Journal: Journal of Clinical and Experimental Hepatology

Year: 2020

Volume: 10

Issue: 1

Pages: 17-29

Print publication date: 01/01/2020

Online publication date: 15/06/2019

Acceptance date: 10/06/2019

ISSN (print): 0973-6883

ISSN (electronic): 2213-3453

Publisher: Elsevier BV

URL: https://doi.org/10.1016/j.jceh.2019.06.001

DOI: 10.1016/j.jceh.2019.06.001

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