Metabolomic profiles of hepatocellular carcinoma in a European prospective cohort

Anne Fages (1, 2) , Talita Duarte-Salles (3) , Magdalena Stepien (3) , Pietro Ferrari (4, 3) , Veronika Fedirko (5) , Clément Pontoizeau (2) , Antonia Trichopoulou (6) , Krasimira Aleksandrova (7) , Anne Tjønneland (8) , Anja Olsen (9) , Françoise Clavel-Chapelon (10) , Marie-Christine Boutron-Ruault (10, 11) , Gianluca Severi (12) , Rudolf Kaaks (13) , Tilman Kuhn (14) , Anna Floegel (15) , Heiner Boeing (16) , Pagona Lagiou (6, 17) , Christina Bamia (18) , Dimitrios Trichopoulos (6) , Domenico Palli (19) , Valeria Pala (20) , Salvatore Panico (21) , Rosario Tumino (22) , Paolo Vineis (23) , H. Bas Bueno-De-Mesquita (24) , Petra H. Peeters (25, 26) , Elisabete Weiderpass (27, 28, 29) , Antonio Agudo (30) , Esther Molina-Montes (31, 32) , José María Huerta (33, 34) , Eva Ardanaz (32, 35) , Miren Dorronsoro (36) , Klas Sjöberg (37) , Bodil Ohlsson (38) , Kay-Tee Khaw (39) , Nick Wareham (40) , Ruth C. Travis (41) , Julie A. Schmidt (42) , Amanda Cross (43) , Marc Gunter (44) , Elio Riboli (45) , Augustin Scalbert (46) , Isabelle Romieu (47) , Benedicte Elena-Herrmann (1) , Mazda Jenab (5)

1 ISA NMR Methods for Metabolism - Methodes RMN en métabolomique (2014-2018)
2 ISA - Centre de RMN à très hauts champs
3 CIRC - IARC - Centre International de Recherche contre le Cancer - International Agency for Research on Cancer
4
5 IACR - International Agency for Cancer Research
6 Department of Hygiene, Epidemiology and Medical Statistics
7 Department of Epidemiology
8 Institute of Cancer Epidemiology, Danish Cancer Society
9 UCPH FOOD - Department of Food Science [Copenhagen]
10 CESP - Centre de recherche en épidémiologie et santé des populations
11 IGR - Institut Gustave Roussy
12 HuGeF - Human Genetics Foundation
13 Division of Cancer Epidemiology
14 Thermo Fisher Scientific
15 Department of Epidemiology
16 Department of Epidemiology
17 Department of Epidemiology
18 WHO Collaborating Center for Food and Nutrition Policies, Department of Hygiene
19 Molecular and Nutritional Epidemiology Unit
20 Nutritional Epidemiology Unit
21 Department of Clinical and Experimental Medicine
22 Cancer Registry and Histopathology Unit
23 Department of Epidemiology and Biostatistics
24 RIVM - National Institute for Public Health and the Environment [Bilthoven]
25 Julius Center for Health Sciences and Primary Care
26 Department of Epidemiology and Biostatistics
27 Department of Community Medicine
28 Department of Research
29 Department of Medical Epidemiology and Biostatistics
30 Institut Català d'Oncologia
31 Andalusian School of Public Health [Granada]
32 CIBERESP - Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública = Consortium for Biomedical Research of Epidemiology and Public Health
33 Danish Cancer Society Research Center
34 Department of Epidemiology
35 Sección de Epidemiología de Enfermedades No Transmisibles
36 Epidemiology and Health Information
37 Volvo
38 Skane University Hospital [Lund]
39 University of Cambridge School of Clinical Medicine
40 MRC epidemiology Unit
41 Cancer Epidemiology Unit
42 LIF - Laboratoire d'informatique Fondamentale de Marseille
43 Faculty of Medicine - School of Public Health [London, UK]
44 Department of Chemistry
45 Department of Epidemiology and Biostatistics
46 , Nutrition and Metabolism Section, Biomarkers Group
47 Nutrition and Metabolism Section

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.

Mots clés: IDENTIFY SERUM BIOMARKERS; FATTY LIVER-DISEASE; TISSUE METABOLOMICS; MASS-SPECTROMETRY; RISK-FACTORS; CANCER; NMR; CIRRHOSIS; METABONOMICS; DISCOVERY; Epidemiology; European Prospective Investigation into Cancer and Nutrition; Hepatocellular carcinoma; Liver cancer; Metabolomics; Nuclear magnetic resonance

Domaines: Chimie analytique; Médecine humaine et pathologie

Anne Fages, Talita Duarte-Salles, Magdalena Stepien, Pietro Ferrari, Veronika Fedirko, et al.. Metabolomic profiles of hepatocellular carcinoma in a European prospective cohort. BMC Medicine, 2015, 13 (242), ⟨10.1186/s12916-015-0462-9⟩. ⟨hal-01234339⟩