Metabolomic profiles of hepatocellular carcinoma in a European prospective cohort

BMC Medicine

Mazda Jenab^1,15  Benedicte Elena-Herrmann¹  Isabelle Romieu^1,15  Augustin Scalbert^1,15  Elio Riboli^2,27  Marc Gunter^2,27  Amanda Cross^2,27  Julie A. Schmidt²  Ruth C. Travis²  Nick Wareham^2,22  Kay-Tee Khaw^1,16  Bodil Ohlsson⁸  Klas Sjöberg^1,11  Miren Dorronsoro^1,17  Eva Ardanaz^2,24  José María Huerta^2,20  Esther Molina-Montes^1,10  Antonio Agudo⁴  Elisabete Weiderpass⁵  Petra H. Peeters⁶  H. Bas Bueno-de-Mesquita^1,13  Paolo Vineis^1,19  Rosario Tumino^1,14  Salvatore Panico⁷  Valeria Pala^1,12  Domenico Palli³  Dimitrios Trichopoulos^3,30  Christina Bamia^2,28  Pagona Lagiou^2,26  Heiner Boeing^2,29  Anna Floegel^2,29  Tilman Kuhn^1,18  Rudolf Kaaks^1,18  Gianluca Severi⁹  Marie-Christine Boutron-Ruault^2,21  Françoise Clavel-Chapelon^2,21  Anja Olsen^2,23  Anne Tjønneland^2,23  Krasimira Aleksandrova^2,29  Antonia Trichopoulou^3,30  Clément Pontoizeau¹  Veronika Fedirko^2,25  Pietro Ferrari^1,15  Magdalena Stepien^1,15  Talita Duarte-Salles^1,15  Anne Fages¹ 

[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, Villeurbanne, 69100, France;Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK;Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute – ISPO, Florence, Italy;Unit of Nutrition and Cancer, IDIBELL, Catalan Institute of Oncology-ICO, L’Hospitalet de Llobregat, Barcelona 08908, Spain;Samfundet Folkhälsan, Helsinki, Finland;Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands;Dipartimento di Medicina Clinica e Chirurgia, Federico II University, Naples, Italy;Department of Clinical Sciences, Division of Internal Medicine, Skåne University Hospital, Lund University, Malmö, Sweden;Human Genetics Foundation (HuGeF), Torino, Italy;CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain;Department of Gastroenterology and Nutrition, Skåne University Hospital, Malmö, Sweden;Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, Milano, 20133, Italy;Department of Social & Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia;Cancer Registry and Histopathology Unit, “Civic - M.P. Arezzo” Hospital, Ragusa, Italy;International Agency for Research on Cancer (IARC-WHO), Lyon, France;University of Cambridge School of Clinical Medicine, Clinical Gerontology Unit, Addenbrooke’s Hospital, Cambridge, UK;Public Health Direction and Biodonostia CIBERESP, Basque Regional Health Department, San Sebastian, Spain;Department of Cancer Epidemiology, German Cancer Research Centre, Heidelberg, Germany;MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London, UK;Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain;Université Paris Sud, UMRS 1018, Villejuif, F-94805, France;MRC Epidemiology Unit, University of Cambridge, Cambridge, UK;Diet, Genes and Environment, Danish Cancer Society Research Center, Strandboulevarden 49, Copenhagen, DK 2100, Denmark;Navarre Public Health Institute, Pamplona, Spain;Department of Epidemiology, Rollins School of Public Health, Winship Cancer Institute, Emory University, Atlanta, GA, USA;Department of Epidemiology, Harvard School of Public Health, 677 Huntington Avenue, Boston 02115, MA, USA;Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK;Department of Hygiene, Epidemiology, and Medical Statistics, University of Athens Medical School, 75 M. Asias, Goudi, Athens, GR-115 27, Greece;Department of Epidemiology, German Institute of Human Nutrition (DIfE), Potsdam-Rehbrücke, Germany;Bureau of Epidemiologic Research, Academy of Athens, Kaisareias 13, Athens, GR-115 27, Greece

关键词: Nuclear magnetic resonance;    Metabolomics;    Liver cancer;    Hepatocellular carcinoma;    European Prospective Investigation into Cancer and Nutrition;    Epidemiology;   

Others  :  1227209
DOI  :  10.1186/s12916-015-0462-9

 received in 2015-05-13, accepted in 2015-08-25,  发布年份 2015

【 摘 要 】

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.

【 授权许可】

   
2015 Fages et al.

【 图 表 】

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