Two Metabolomics Phenotypes of Human Hepatocellular Carcinoma in Non-Alcoholic Fatty Liver Disease According to Fibrosis Severity
Non-Alcoholic Fatty Liver Disease (NAFLD) is considered as the forthcoming predominant cause for hepatocellular carcinoma (HCC). NAFLD-HCC may rise in non-cirrhotic livers in 40 to 50% of patients. The aim of this study was to identify different metabolic pathways of HCC according to fibrosis level...
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2021-01-01
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| author | Benjamin Buchard Camille Teilhet Natali Abeywickrama Samarakoon Sylvie Massoulier Juliette Joubert-Zakeyh Corinne Blouin Christelle Reynes Robert Sabatier Anne-Sophie Biesse-Martin Marie-Paule Vasson Armando Abergel Aicha Demidem |
| author_facet | Benjamin Buchard Camille Teilhet Natali Abeywickrama Samarakoon Sylvie Massoulier Juliette Joubert-Zakeyh Corinne Blouin Christelle Reynes Robert Sabatier Anne-Sophie Biesse-Martin Marie-Paule Vasson Armando Abergel Aicha Demidem |
| author_sort | Benjamin Buchard |
| collection | DOAJ |
| description | Non-Alcoholic Fatty Liver Disease (NAFLD) is considered as the forthcoming predominant cause for hepatocellular carcinoma (HCC). NAFLD-HCC may rise in non-cirrhotic livers in 40 to 50% of patients. The aim of this study was to identify different metabolic pathways of HCC according to fibrosis level (F0F1 vs. F3F4). A non-targeted metabolomics strategy was applied. We analyzed 52 pairs of human HCC and adjacent non-tumoral tissues which included 26 HCC developed in severe fibrosis or cirrhosis (F3F4) and 26 in no or mild fibrosis (F0F1). Tissue extracts were analyzed using <sup>1</sup>H-Nuclear Magnetic Resonance spectroscopy. An optimization evolutionary method based on genetic algorithm was used to identify discriminant metabolites. We identified 34 metabolites differentiating the two groups of NAFLD-HCC according to fibrosis level, allowing us to propose two metabolomics phenotypes of NAFLD-HCC. We showed that HCC-F0F1 mainly overexpressed choline derivatives and glutamine, whereas HCC-F3F4 were characterized by a decreased content of monounsaturated fatty acids (FA), an increase of saturated FA and an accumulation of branched amino acids. Comparing HCC-F0F1 and HCC-F3F4, differential expression levels of glucose, choline derivatives and phosphoethanolamine, monounsaturated FA, triacylglycerides were identified as specific signatures. Our metabolomics analysis of HCC tissues revealed for the first time two phenotypes of HCC developed in NAFLD according to fibrosis level. This study highlighted the impact of the underlying liver disease on metabolic reprogramming of the tumor. |
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| issn | 2218-1989 |
| language | English |
| last_indexed | 2024-03-09T04:44:54Z |
| publishDate | 2021-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Metabolites |
| spelling | doaj.art-63ced95260ea40db9076ec1b0fd930ba2023-12-03T13:16:43ZengMDPI AGMetabolites2218-19892021-01-011115410.3390/metabo11010054Two Metabolomics Phenotypes of Human Hepatocellular Carcinoma in Non-Alcoholic Fatty Liver Disease According to Fibrosis SeverityBenjamin Buchard0Camille Teilhet1Natali Abeywickrama Samarakoon2Sylvie Massoulier3Juliette Joubert-Zakeyh4Corinne Blouin5Christelle Reynes6Robert Sabatier7Anne-Sophie Biesse-Martin8Marie-Paule Vasson9Armando Abergel10Aicha Demidem11Department of Digestive and Hepatobiliary Medecine, CHU Clermont-Ferrand, F-63000 Clermont-Ferrand, FranceDepartment of Digestive and Hepatobiliary Medecine, CHU Clermont-Ferrand, F-63000 Clermont-Ferrand, FranceINRA, Human Nutrition Unit, Clermont Auvergne University, F-63000 Clermont-Ferrand, FranceDepartment of Digestive and Hepatobiliary Medecine, CHU Clermont-Ferrand, F-63000 Clermont-Ferrand, FranceDepartment of Anatomo-pathology, CHU Clermont Ferrand, F-63000 Clermont-Ferrand, FranceDepartment of Anatomo-pathology, CHU Clermont Ferrand, F-63000 Clermont-Ferrand, FranceLaboratory of Biostatistics, Computer Science and Pharmaceutical Physics, UMR 5203, Faculty of Pharmacy, F-34 093 Montpellier, FranceLaboratory of Biostatistics, Computer Science and Pharmaceutical Physics, UMR 5203, Faculty of Pharmacy, F-34 093 Montpellier, FranceTeam RMN-START, Clermont Auvergne University, F-63000 Clermont-Ferrand, FranceINRA, Human Nutrition Unit, Clermont Auvergne University, F-63000 Clermont-Ferrand, FranceDepartment of Digestive and Hepatobiliary Medecine, CHU Clermont-Ferrand, F-63000 Clermont-Ferrand, FranceINRA, Human Nutrition Unit, Clermont Auvergne University, F-63000 Clermont-Ferrand, FranceNon-Alcoholic Fatty Liver Disease (NAFLD) is considered as the forthcoming predominant cause for hepatocellular carcinoma (HCC). NAFLD-HCC may rise in non-cirrhotic livers in 40 to 50% of patients. The aim of this study was to identify different metabolic pathways of HCC according to fibrosis level (F0F1 vs. F3F4). A non-targeted metabolomics strategy was applied. We analyzed 52 pairs of human HCC and adjacent non-tumoral tissues which included 26 HCC developed in severe fibrosis or cirrhosis (F3F4) and 26 in no or mild fibrosis (F0F1). Tissue extracts were analyzed using <sup>1</sup>H-Nuclear Magnetic Resonance spectroscopy. An optimization evolutionary method based on genetic algorithm was used to identify discriminant metabolites. We identified 34 metabolites differentiating the two groups of NAFLD-HCC according to fibrosis level, allowing us to propose two metabolomics phenotypes of NAFLD-HCC. We showed that HCC-F0F1 mainly overexpressed choline derivatives and glutamine, whereas HCC-F3F4 were characterized by a decreased content of monounsaturated fatty acids (FA), an increase of saturated FA and an accumulation of branched amino acids. Comparing HCC-F0F1 and HCC-F3F4, differential expression levels of glucose, choline derivatives and phosphoethanolamine, monounsaturated FA, triacylglycerides were identified as specific signatures. Our metabolomics analysis of HCC tissues revealed for the first time two phenotypes of HCC developed in NAFLD according to fibrosis level. This study highlighted the impact of the underlying liver disease on metabolic reprogramming of the tumor.https://www.mdpi.com/2218-1989/11/1/54hepatocarcinomafibrosisnon-alcoholic fatty liver diseasenuclear magnetic resonancemetabolomics |
| spellingShingle | Benjamin Buchard Camille Teilhet Natali Abeywickrama Samarakoon Sylvie Massoulier Juliette Joubert-Zakeyh Corinne Blouin Christelle Reynes Robert Sabatier Anne-Sophie Biesse-Martin Marie-Paule Vasson Armando Abergel Aicha Demidem Two Metabolomics Phenotypes of Human Hepatocellular Carcinoma in Non-Alcoholic Fatty Liver Disease According to Fibrosis Severity Metabolites hepatocarcinoma fibrosis non-alcoholic fatty liver disease nuclear magnetic resonance metabolomics |
| title | Two Metabolomics Phenotypes of Human Hepatocellular Carcinoma in Non-Alcoholic Fatty Liver Disease According to Fibrosis Severity |
| title_full | Two Metabolomics Phenotypes of Human Hepatocellular Carcinoma in Non-Alcoholic Fatty Liver Disease According to Fibrosis Severity |
| title_fullStr | Two Metabolomics Phenotypes of Human Hepatocellular Carcinoma in Non-Alcoholic Fatty Liver Disease According to Fibrosis Severity |
| title_full_unstemmed | Two Metabolomics Phenotypes of Human Hepatocellular Carcinoma in Non-Alcoholic Fatty Liver Disease According to Fibrosis Severity |
| title_short | Two Metabolomics Phenotypes of Human Hepatocellular Carcinoma in Non-Alcoholic Fatty Liver Disease According to Fibrosis Severity |
| title_sort | two metabolomics phenotypes of human hepatocellular carcinoma in non alcoholic fatty liver disease according to fibrosis severity |
| topic | hepatocarcinoma fibrosis non-alcoholic fatty liver disease nuclear magnetic resonance metabolomics |
| url | https://www.mdpi.com/2218-1989/11/1/54 |
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