Fages, AnneDuarte-Salles, TalitaStepien, MagdalenaFerrari, PietroFedirko, VeronikaPontoizeau, ClémentTrichopoulou, AntoniaAleksandrova, KrasimiraTjønneland, AnneOlsen, AnjaClavel-Chapelon, FrançoiseBoutron-Ruault, Marie-ChristineSeveri, GianlucaKaaks, RudolfKuhn, TilmanFloegel, AnnaBoeing, HeinerLagiou, PagonaBamia, ChristinaTrichopoulos, DimitriosPalli, DomenicoPala, ValeriaPanico, SalvatoreTumino, RosarioVineis, PaoloBueno-de-Mesquita, H BasPeeters, Petra HWeiderpass, ElisabeteAgudo, AntonioMolina-Montes, EstherHuerta, José MaríaArdanaz, EvaDorronsoro, MirenSjöberg, KlasOhlsson, BodilKhaw, Kay-TeeWareham, NickTravis, Ruth CSchmidt, Julie ACross, AmandaGunter, MarcRiboli, ElioScalbert, AugustinRomieu, IsabelleElena-Herrmann, BenedicteJenab, Mazda2015-12-022015-12-022015-09-23Fages A, Duarte-Salles T, Stepien M, Ferrari P, Fedirko V, Pontoizeau C, et al. Metabolomic profiles of hepatocellular carcinoma in a European prospective cohort. BMC Med 2015;13(1):242http://hdl.handle.net/10668/2102JOURNAL ARTICLE;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. CONCLUSION 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.spaEpidemiologyEuropean Prospective Investigation into Cancer and NutritionHepatocellular carcinomaLiver cancerMetabolomicsNuclear magnetic resonanceCarcinoma HepatocelularNeoplasias HepáticasMetabolómicaEstudios ProspectivosMedical Subject Headings::Diseases::Neoplasms::Neoplasms by Histologic Type::Neoplasms, Glandular and Epithelial::Carcinoma::Adenocarcinoma::Carcinoma, HepatocellularMedical Subject Headings::Diseases::Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Liver NeoplasmsMedical Subject Headings::Disciplines and Occupations::Natural Science Disciplines::Biological Science Disciplines::Biochemistry::MetabolomicsMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies::Longitudinal Studies::Prospective StudiesMedical Subject Headings::Psychiatry and Psychology::Behavior and Behavior Mechanisms::Behavior::Drinking Behavior::Alcohol DrinkingMedical Subject Headings::Diseases::Nutritional and Metabolic Diseases::Metabolic Diseases::Glucose Metabolism Disorders::Diabetes MellitusMedical Subject Headings::Diseases::Nutritional and Metabolic Diseases::Nutrition Disorders::Overnutrition::ObesityMedical Subject Headings::Psychiatry and Psychology::Behavior and Behavior Mechanisms::Behavior::Habits::Smokingresearch article26399231open access10.1186/s12916-015-0462-91741-7015PMC4581424