Metallomic profile in non-cirrhotic hepatocellular carcinoma supports a phenomenon of metal metabolism adaptation in tumor cells

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Cano L.
Bertani S.
Island M.-L.
Cerapio J.P.
Ruiz E.
Pineau P.
Monbet V.
Boudjema K.
Taxa L.
Casavilca-Zambrano S.
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Nature Research
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We have previously described a form of hepatocellular carcinoma (HCC) in non-cirrhotic liver (HCC-NC) developed by Peruvian patients. We analyzed the metallomic profile in hepatic tissues from two independent cohorts exhibiting HCC-NC. Clinical, histopathological data, and HCC and non-tumoral liver (NTL) samples of 38 Peruvian and 38 French HCC-NC patients, were studied. Twelve metals were quantified using ICP/MS: Mn, Fe, Cu, Co, Zn, As, Se, Rb, Mo, Cd, Pb, and Sn. Associations between metals and survival were assessed. Our data showed significant differences between cohorts. Mean ages were 40.6 ± 20, 67.5 ± 9 years old for Peruvians and French, respectively. Fifty percent of the Peruvian patients were positive for the HBsAg, versus 3% in French patients. Mn, Cu, Zn, As, Se, Rb, Mo, Cd, Sn metal concentrations were higher in NTL of Peruvians. Importantly, metal concentrations were lower in HCC areas compared to NTL tissues in both cohorts, except for Cu for which mean concentration was higher in HCC (p < 0.05). Se concentration in HCC was associated with extended survival only in Peruvians. Our data, obtained in Peruvian and French HCC-NC cohorts, highlights similarity in the metallomic profile of HCC compared to NTL during the hepatic tumorigenesis in these specific groups of patients. © 2021, The Author(s).
This study was funded by the French National Alliance for Life Sciences and Health (ENV201408); LC was a recipient of a doctoral fellowship from French National Research Institute for Sustainable Development (IRD) (EMHE-ARTS-2016-878573B); JPC was a recipient of a doctoral fellowship from the Peruvian National Council for Science and Technology (212-2015-FONDECYT); SB has received funding from the European Union’s Horizon 2020 Framework program under the Marie Sk?odowska-Curie Actions 823935 and from the Alliance pour les Sciences de la Vie et de la Santé (AVIESAN), ITMO Cancer ENV201408, and LC, ER, and SCZ have received funding from the World Bank Group and FONDECYT-CONCYTEC 016-2018-FONDECYT/BM. The authors are grateful to Karina Cancino, Danny Cordova (INEN Cancer Research Biobank), Patricia Leroyer (NUMECAN), Alain Fautrel, Marine Seffals, Gevorg Ghukasyan (H2P2 platform). They also thank Dr Anne Corlu for the critical reviewing of the manuscript.
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metal metabolism, hepatocellular carcinoma