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Metabolomic profiles of hepatocellular carcinoma in a European prospective cohort

Fages A 1 , Duarte-Salles T 2 , Stepien M 2 , Ferrari P 2 , Fedirko V 3 , Pontoizeau C 1 Show all authors , Trichopoulou A 4 , Aleksandrova K 5 , Tjønneland A 6 , Olsen A 6 , Clavel-Chapelon F 7 , Boutron-Ruault MC 7 , Severi G 8 , Kaaks R 9 , Kuhn T 9 , Floegel A 5 , Boeing H 5 , Lagiou P 10 , Bamia C 10 , Trichopoulos D 4 , Palli D 11 , Pala V 12 , Panico S 13 , Tumino R 14 , Vineis P 8 , Bueno-de-Mesquita HB 15 , Peeters PH 16 , Weiderpass E 17 , Agudo A 18 , Molina-Montes E 19 , Huerta JM 20 , Ardanaz E 20 , Dorronsoro M 21 , Sjöberg K 22 , Ohlsson B 23 , Khaw KT 24 , Wareham N 25 , Travis RC 26 , Schmidt JA 26 , Cross A 27 , Gunter M 27 , Riboli E 27 , Scalbert A 2 , Romieu I 2 , Elena-Herrmann B 28 , Jenab M 29

Affiliations 

  • 1 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
  • 2 International Agency for Research on Cancer (IARC-WHO), Lyon, France
  • 3 Department of Epidemiology, Rollins School of Public Health, Winship Cancer Institute, Emory University, Atlanta, GA, USA
  • 4 Hellenic Health Foundation, Alexandroupoleos 23, GR-115 27, Athens, Greece
  • 5 Department of Epidemiology, German Institute of Human Nutrition (DIfE), Potsdam-Rehbrücke, Germany
  • 6 Diet, Genes and Environment, Danish Cancer Society Research Center, Strandboulevarden 49, DK 2100, Copenhagen, Denmark
  • 7 INSERM, Centre for Research in Epidemiology and Population Health (CESP), U1018, Nutrition, Hormones and Women's Health Team, F-94805, Villejuif, France
  • 8 Human Genetics Foundation (HuGeF), Torino, Italy
  • 9 Department of Cancer Epidemiology, German Cancer Research Centre, Heidelberg, Germany
  • 10 Department of Hygiene, Epidemiology, and Medical Statistics, University of Athens Medical School, 75 M. Asias, Goudi, GR-115 27, Athens, Greece
  • 11 Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute - ISPO, Florence, Italy
  • 12 Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133, Milano, Italy
  • 13 Dipartimento di Medicina Clinica e Chirurgia, Federico II University, Naples, Italy
  • 14 Cancer Registry and Histopathology Unit, "Civic - M.P. Arezzo" Hospital, Ragusa, Italy
  • 15 Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands
  • 16 MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London, UK
  • 17 Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, The Arctic University of Norway, Tromsø, Norway
  • 18 Unit of Nutrition and Cancer, IDIBELL, Catalan Institute of Oncology-ICO, L'Hospitalet de Llobregat, Barcelona, 08908, Spain
  • 19 Escuela Andaluza de Salud Pública, Instituto de Investigación Biosanitaria ibs.GRANADA, Hospitales Universitarios de Granada/Universidad de Granada, Granada, Spain
  • 20 CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain
  • 21 Public Health Direction and Biodonostia CIBERESP, Basque Regional Health Department, San Sebastian, Spain
  • 22 Department of Clinical Sciences, Lund University, Malmö, Sweden
  • 23 Department of Clinical Sciences, Division of Internal Medicine, Skåne University Hospital, Lund University, Malmö, Sweden
  • 24 University of Cambridge School of Clinical Medicine, Clinical Gerontology Unit, Addenbrooke's Hospital, Cambridge, UK
  • 25 MRC Epidemiology Unit, University of Cambridge, Cambridge, UK
  • 26 Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK
  • 27 Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK
  • 28 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. [email protected]
  • 29 International Agency for Research on Cancer (IARC-WHO), Lyon, France. [email protected]
BMC Med, 2015 Sep 23;13:242.
PMID: 26399231 DOI: 10.1186/s12916-015-0462-9

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.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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