Stepien, Magdalena and Keski-Rahkonen, Pekka and Kiss, Agneta and Robinot, Nivonirina and Duarte-Salles, Talita and Murphy, Neil and Perlemuter, Gabriel and Viallon, Vivian and Tjonneland, Anne and Rostgaard-Hansen, Agnetha Linn and Dahm, Christina C. and Overvad, Kim and Boutron-Ruault, Marie-Christine and Mancini, Francesca Romana and Mahannat-Saleh, Yahya and Aleksandrova, Krasimira and Kaaks, Rudolf and Kuehn, Tilman and Trichopoulou, Antonia and Karakatsani, Anna and Panico, Salvatore and Tumino, Rosario and Palli, Domenico and Tagliabue, Giovanna and Naccarati, Alessio and Vermeulen, Roel C. H. and Bueno-de-Mesquita, Hendrik Bastiaan and Weiderpass, Elisabete and Skeie, Guri and Ramon Quiros, Jose and Ardanaz, Eva and Mokoroa, Olatz and Sala, Nuria and Sanchez, Maria-Jose and Maria Huerta, Jose and Winkvist, Anna and Harlid, Sophia and Ohlsson, Bodil and Sjoberg, Klas and Schmidt, Julie A. and Wareham, Nick and Khaw, Kay-Tee and Ferrari, Pietro and Rothwell, Joseph A. and Gunter, Marc and Riboli, Elio and Scalbert, Augustin and Jenab, Mazda (2021) Metabolic perturbations prior to hepatocellular carcinoma diagnosis: Findings from a prospective observational cohort study. International Journal of Cancer, 148 (3). pp. 609-625. ISSN 0020-7136, DOI https://doi.org/10.1002/ijc.33236.
Full text not available from this repository.Abstract
Hepatocellular carcinoma (HCC) development entails changes in liver metabolism. Current knowledge on metabolic perturbations in HCC is derived mostly from case-control designs, with sparse information from prospective cohorts. Our objective was to apply comprehensive metabolite profiling to detect metabolites whose serum concentrations are associated with HCC development, using biological samples from within the prospective European Prospective Investigation into Cancer and Nutrition (EPIC) cohort (>520 000 participants), where we identified 129 HCC cases matched 1:1 to controls. We conducted high-resolution untargeted liquid chromatography-mass spectrometry-based metabolomics on serum samples collected at recruitment prior to cancer diagnosis. Multivariable conditional logistic regression was applied controlling for dietary habits, alcohol consumption, smoking, body size, hepatitis infection and liver dysfunction. Corrections for multiple comparisons were applied. Of 9206 molecular features detected, 220 discriminated HCC cases from controls. Detailed feature annotation revealed 92 metabolites associated with HCC risk, of which 14 were unambiguously identified using pure reference standards. Positive HCC-risk associations were observed forN1-acetylspermidine, isatin,p-hydroxyphenyllactic acid, tyrosine, sphingosine,l,l-cyclo(leucylprolyl), glycochenodeoxycholic acid, glycocholic acid and 7-methylguanine. Inverse risk associations were observed for retinol, dehydroepiandrosterone sulfate, glycerophosphocholine, gamma-carboxyethyl hydroxychroman and creatine. Discernible differences for these metabolites were observed between cases and controls up to 10 years prior to diagnosis. Our observations highlight the diversity of metabolic perturbations involved in HCC development and replicate previous observations (metabolism of bile acids, amino acids and phospholipids) made in Asian and Scandinavian populations. These findings emphasize the role of metabolic pathways associated with steroid metabolism and immunity and specific dietary and environmental exposures in HCC development.
| Item Type: | Article |
|---|---|
| Funders: | French National Cancer Institute (L'Institut National du Cancer; INCA) [Grant No: 2014-1-RT-02-CIRC-1], European Commission European Commission Joint Research Centre, International Agency for Research on Cancer, Danish Cancer Society, Ligue nationale contre le cancer, Institut Gustave Roussy, Mutuelle Generale de l'Education Nationale, Institut National de la Sante et de la Recherche Medicale (Inserm), Helmholtz Association, Federal Ministry of Education & Research (BMBF), Hellenic Health Foundation (Greece), Fondazione AIRC per la ricerca sul cancro, National Research Council, AIRE-ONLUS Ragusa, Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Netherlands Organization for Scientific Research (NWO), World Cancer Research Fund International (WCRF), Netherlands Government, etc |
| Uncontrolled Keywords: | Hepatocellular carcinoma; Prospective observational cohort; Untargeted metabolomics |
| Subjects: | R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer) |
| Divisions: | Faculty of Medicine |
| Depositing User: | Ms Zaharah Ramly |
| Date Deposited: | 14 Sep 2022 02:33 |
| Last Modified: | 14 Sep 2022 02:33 |
| URI: | http://eprints.um.edu.my/id/eprint/34710 |
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