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Characterisation of the serum metabolic signature of cholangiocarcinoma in a United Kingdom cohort

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Title: Characterisation of the serum metabolic signature of cholangiocarcinoma in a United Kingdom cohort
Authors: 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
Item Type: Journal Article
Abstract: 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.
Issue Date: Jan-2020
Date of Acceptance: 10-Jun-2019
URI: http://hdl.handle.net/10044/1/72084
DOI: 10.1016/j.jceh.2019.06.001
ISSN: 0973-6883
Publisher: Elsevier BV
Start Page: 17
End Page: 29
Journal / Book Title: Journal of Clinical and Experimental Hepatology
Volume: 10
Issue: 1
Copyright Statement: © 2019 Elsevier Ltd. All rights reserved. This manuscript is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International Licence http://creativecommons.org/licenses/by-nc-nd/4.0/
Sponsor/Funder: AMMF
Wellcome Trust
Imperial Health Charity
Imperial College Trust
Imperial Health Charity
Royal College of Physicians
Wellcome Trust
Funder's Grant Number: N/A
097816/Z/11/ZR
Fund 5101
N/A
Fund 5101
N/A
105603/Z/14/Z
Keywords: Science & Technology
Life Sciences & Biomedicine
Gastroenterology & Hepatology
mass spectroscopy
cholangiocarcinoma
metabolic finger print
metabolomics
diagnostic biomarkers
MAGNETIC-RESONANCE-SPECTROSCOPY
PRIMARY BILIARY-CIRRHOSIS
BILE
LYSOPHOSPHATIDYLCHOLINE
PHOSPHATIDYLCHOLINE
MUTATIONS
ABC, ATP-binding cassette
CCA, cholangiocarcinoma
CRP, C-reactive protein
DDA, data-dependent acquisition
ESI, electrospray ionisation
GC–MS, gas chromatography–mass spectroscopy
HCC, hepatocellular carcinoma
HILIC, hydrophilic interaction liquid chromatography
HPO, hydrogen peroxide
LC-MS, liquid chromatography–mass spectroscopy
MDR3, multidrug-resistant protein 3
MS, mass spectroscopy
NMR, nuclear magnetic resonance
OPLS, orthogonal projections to latent structures
OPLS-DA, orthogonal projections to latent structures discriminant analysis
PBC, primary biliary cirrhosis
PC, phosphatidylcholine
PCA, principal component analysis
PE, phosphatidylethanolamine
PSC, primary sclerosing cholangitis
UPLC, Ultraperformance liquid chromatography
VIP, variable importance in projection
cholangiocarcinoma
diagnostic biomarkers
mass spectroscopy
metabolic finger print
metabolomics
Publication Status: Published
Online Publication Date: 2019-06-15
Appears in Collections:Faculty of Engineering
Department of Metabolism, Digestion and Reproduction
Electrical and Electronic Engineering