Characterisation of the Serum Metabolic Signature of Cholangiocarcinoma in a United Kingdom Cohort.
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
Journal
Journal of clinical and experimental hepatology
ISSN: 0973-6883
Titre abrégé: J Clin Exp Hepatol
Pays: India
ID NLM: 101574137
Informations de publication
Date de publication:
Historique:
received:
19
12
2018
accepted:
10
06
2019
entrez:
7
2
2020
pubmed:
7
2
2020
medline:
7
2
2020
Statut:
ppublish
Résumé
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. 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. 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. 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.
Sections du résumé
BACKGROUND
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
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
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
CONCLUSIONS
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.
Identifiants
pubmed: 32025163
doi: 10.1016/j.jceh.2019.06.001
pii: S0973-6883(19)30155-0
pmc: PMC6995894
doi:
Types de publication
Journal Article
Langues
eng
Pagination
17-29Subventions
Organisme : Cancer Research UK
ID : 26813
Pays : United Kingdom
Informations de copyright
© 2019 Indian National Association for Study of the Liver. Published by Elsevier B.V. All rights reserved.
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