Munirah Alsaleh1, Zoe Leftley1, Thomas A Barbera1, Larry K Koomson1, Abigail Zabron1, Mary M E Crossey1, Helen L Reeves2, Matthew Cramp3, Stephen Ryder4, Shaun Greer5, Martin Prince5, Paiboon Sithithaworn6, Mohamed Shariff1, Narong Khuntikeo6, Watcharin Loilome6, Puangrat Yongvanit6, Yi-Liang Shen1,7, I Jane Cox8, Roger Williams8,9, Christopher A Wadsworth1, Elaine Holmes1, Kathryn Nash10, Simon D Taylor-Robinson1. 1. Division of Surgery and Cancer, Imperial College London, London, W2 INY, United Kingdom. 2. Northern Institute for Cancer Research, Paul O'Gorman Building, Medical School, University of Newcastle, Framlington Place, Newcastle Upon Tyne, NE2 4HH, United Kingdom. 3. Liver Unit, Derriford Hospital, Derriford Road, Crownhill, Plymouth, Devon, PL6 8DH, United Kingdom. 4. Nottingham Digestive Diseases Centre, University of Nottingham and NIHR Biomedical Research Unit, Nottingham University Hospitals NHS Trust, Queen's Medical Centre, Nottingham, NG7 2UH, United Kingdom. 5. Centre for Hepatology, Manchester Royal Infirmary, Oxford Road, Manchester, M13 9WL, United Kingdom. 6. Cholangiocarcinoma Research Centre, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand. 7. Department of Radiation Oncology, Chang Gung Memorial Hospital and Chang Gung University, No.5, Fuxing Street, Guishan District, Taoyuan, 333, Taiwan. 8. Institute of Hepatology London, Foundation for Liver Research, 111 Coldharbour Lane, London, SE5 9NT, United Kingdom. 9. Faculty of Life Sciences & Medicine, King's College London, United Kingdom. 10. Liver Unit, Southampton General Hospital, Tremona Rd, Southampton, Hampshire, SO16 6YD, United Kingdom.
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.
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.
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