Metabolomic profiles of hepatocellular carcinoma in a European prospective cohort

• Type of Material: Article
• Authors: Anne Fages, Université de Lyon; Talita Duarte-Salles, International Agency for Research on Cancer (IARC-WHO); Magdalena Stepien, International Agency for Research on Cancer (IARC-WHO); Pietro Ferrari, International Agency for Research on Cancer (IARC-WHO) Cancer; Veronika Fedirko, Emory University; Clément Pontoizeau, Université de Lyon; Antonia Trichopoulou, Hellenic Health Foundation; Krasimira Aleksandrova, German Institute of Human Nutrition (DIfE); Anne Tjønneland, Danish Cancer Society Research Center; Anja Olsen, Danish Cancer Society Research Center; Françoise Clavel-Chapelon, Hormones and Women’s Health Team; Marie-Christine Boutron-Ruault, Hormones and Women’s Health Team; Gianluca Severi, Human Genetics Foundation (HuGeF); Rudolf Kaaks, German Cancer Research Centre; Tilman Kuhn, German Cancer Research Centre; Anna Floegel, German Institute of Human Nutrition (DIfE); Heiner Boeing, German Institute of Human Nutrition (DIfE); Pagona Lagiou, University of Athens Medical School; Christina Bamia, University of Athens Medical School; Dimitrios Trichopoulos, Harvard School of Public Health; Domenico Palli, Cancer Research and Prevention Institute – ISPO; Valeria Pala, Fondazione IRCCS Istituto Nazionale dei Tumori; Salvatore Panico, Federico II University; Rosario Tumino, “Civic - M.P. Arezzo” Hospital; Paolo Vineis, Human Genetics Foundation (HuGeF); H. Bas Bueno-de-Mesquita, National Institute for Public Health and the Environment (RIVM); Petra H. Peeters, Imperial College London; Elisabete Weiderpass, University Medical Center Utrecht; Antonio Agudo, L’Hospitalet de Llobregat; Esther Molina-Montes, Universidad de Granada; José María Huerta, CIBER Epidemiología y Salud Pública (CIBERESP); Eva Ardanaz, CIBER Epidemiología y Salud Pública (CIBERESP); Miren Dorronsoro, Basque Regional Health Department; Klas Sjöberg, Lund University; Bodil Ohlsson, Lund University; Kay-Tee Khaw, Addenbrooke’s Hospital; Nick Wareham, University of Cambridge; Ruth C. Travis, University of Oxford; Julie A. Schmidt, University of Oxford; Amanda Cross, Imperial College London; Marc Gunter, Imperial College London; Elio Riboli, Imperial College London; Augustin Scalbert, International Agency for Research on Cancer (IARC-WHO); Isabelle Romieu, International Agency for Research on Cancer (IARC-WHO); Benedicte Elena-Herrmann, Université de Lyon; Mazda Jenab, International Agency for Research on Cancer (IARC-WHO)
• Language: English
• Date: 2015-12
• Publisher: BioMed Central
• Publication Version: Final Published Version
• Copyright Statement: © Fages et al. 2015
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1186/s12916-015-0462-9
• Title of Journal or Parent Work: BMC Medicine
• ISSN: 1741-7015
• Volume: 13
• Issue: 1
• Grant/Funding Information: This work was supported by the French National Cancer Institute (L’Institut National du Cancer; INCA; grant number 2009-139; PI: M. Jenab).; The national cohorts are supported by Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, and Institut National de la Santé et de la Recherche Médicale (INSERM) (France); Deutsche Krebshilfe, Deutsches Krebsforschungszentrum (DKFZ), and Federal Ministry of Education and Research (Germany); Hellenic Health Foundation (Greece); Italian Association for Research on Cancer (AIRC), National Research Council, Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy, and AIRE-ONLUS Ragusa, AVIS Ragusa, Sicilian Government (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), and Statistics Netherlands (the Netherlands); European Research Council (ERC; grant number ERC-2009-AdG 232997) and Nordforsk, and Nordic Center of Excellence Programme on Food, Nutrition and Health (Norway); Health Research Fund (FIS), Regional Governments of Andalucía, Asturias, Basque Country, Murcia (No. 6236) and Navarra, and ISCIII RETIC (RD06/0020) (Spain); Swedish Cancer Society, Swedish Scientific Council, and Regional Government of Skåne and Västerbotten (Sweden); Cancer Research UK, Medical Research Council, Stroke Association, British Heart Foundation, Department of Health, Food Standards Agency, and Wellcome Trust (UK).; The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer.; AF received financial support (BDI fellowship) from the Centre National de la Recherche Scientifique (CNRS) and Bruker Biospin.
• Keywords: Nuclear magnetic resonance; Liver cancer; Epidemiology; European Prospective Investigation into Cancer and Nutrition; Hepatocellular carcinoma; Metabolomics

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. 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.