title: Metabolomic profiles of hepatocellular carcinoma in a European prospective cohort.
abstract: BACKGROUND
  Hepatocellular carcinoma (HCC), the most prevalent form of liver cancer, is difficult to diagnose and has limited treatment options with a low survival rate. Aside from a few key risk factors, such as hepatitis, high alcohol consumption, smoking, obesity, and diabetes, there is incomplete etiologic understanding of the disease and little progress in identification of early risk biomarkers.
  
  
  METHODS
  To address these aspects, an untargeted nuclear magnetic resonance metabolomic approach was applied to pre-diagnostic serum samples obtained from first incident, primary HCC cases (n = 114) and matched controls (n = 222) identified from amongst the participants of a large European prospective cohort.
  
  
  RESULTS
  A metabolic pattern associated with HCC risk comprised of perturbations in fatty acid oxidation and amino acid, lipid, and carbohydrate metabolism was observed. Sixteen metabolites of either endogenous or exogenous origin were found to be significantly associated with HCC risk. The influence of hepatitis infection and potential liver damage was assessed, and further analyses were made to distinguish patterns of early or later diagnosis.
  
  
  CONCLUSIONS
  Our results show clear metabolic alterations from early stages of HCC development with application for better etiologic understanding, prevention, and early detection of this increasingly common cancer.
authors.affiliation: Institut des Sciences Analytiques, Centre de RMN à très hauts champs, CNRS/ENS Lyon/UCB Lyon-1, Université de Lyon, 5 rue de la Doua, 69100, Villeurbanne, France.
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authors.affiliation: Institut des Sciences Analytiques, Centre de RMN à très hauts champs, CNRS/ENS Lyon/UCB Lyon-1, Université de Lyon, 5 rue de la Doua, 69100, Villeurbanne, France.
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authors.affiliation: INSERM, Centre for Research in Epidemiology and Population Health (CESP), U1018, Nutrition, Hormones and Women's Health Team, F-94805, Villejuif, France.|Université Paris Sud, UMRS 1018, F-94805, Villejuif, France.|Institut Gustave Roussy, F-94805, Villejuif, France.
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authors.affiliation: Department of Hygiene, Epidemiology, and Medical Statistics, University of Athens Medical School, 75 M. Asias, Goudi, GR-115 27, Athens, Greece.|Department of Epidemiology, Harvard School of Public Health, 677 Huntington Avenue, Boston, MA, 02115, USA.
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authors.affiliation: Hellenic Health Foundation, Alexandroupoleos 23, GR-115 27, Athens, Greece.|Bureau of Epidemiologic Research, Academy of Athens, Kaisareias 13, GR-115 27, Athens, Greece.|Department of Epidemiology, Harvard School of Public Health, 677 Huntington Avenue, Boston, MA, 02115, USA.
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authors.affiliation: Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.|Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, The Netherlands.|Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.|Department of Social & Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
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authors.affiliation: Institut des Sciences Analytiques, Centre de RMN à très hauts champs, CNRS/ENS Lyon/UCB Lyon-1, Université de Lyon, 5 rue de la Doua, 69100, Villeurbanne, France. benedicte.elena@ens-lyon.fr.
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mesh_terms: D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000235:genetics*; D016022:Case-Control Studies; D015331:Cohort Studies; D055088:Early Detection of Cancer; D005060:Europe; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D055432:Metabolomics / Q000379:methods*; D008875:Middle Aged; D009765:Obesity / Q000150:complications; D011446:Prospective Studies; D012307:Risk Factors