The altered serum lipidome and its diagnostic potential for Non-Alcoholic Fatty Liver (NAFL)-associated hepatocellular carcinoma
Background: Non-alcoholic fatty liver disease (NAFLD) is affecting more people globally. Indeed, NAFLD is a spectrum of metabolic dysfunctions that can progress to hepatocellular carcinoma (NAFLD-HCC). This development can occur in a non-cirrhotic liver and thus, often lack clinical surveillance. Th...
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Elsevier
2021-11-01
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| Series: | EBioMedicine |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396421004552 |
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| author | Monika Lewinska, PhD Alvaro Santos-Laso, PhD Enara Arretxe, PhD Cristina Alonso, PhD Ekaterina Zhuravleva, PhD Raul Jimenez-Agüero, MD, PhD Emma Eizaguirre, MD, PhD María Jesús Pareja, MD, PhD Manuel Romero-Gómez, MD, PhD Marco Arrese Jimenez, MD, PhD Malte P. Suppli, MD, PhD Filip K. Knop, MD, PhD Stine Karlsen Oversoe, MD, PhD Gerda Elisabeth Villadsen, MD, PhD Thomas Decaens, MD, PhD Flair Jose Carrilho, MD, PhD Claudia PMS de Oliveira, MD, PhD Bruno Sangro, MD, PhD Rocio I.R. Macias, MD, PhD Jesus M. Banales, PhD Jesper B. Andersen, PhD |
| author_facet | Monika Lewinska, PhD Alvaro Santos-Laso, PhD Enara Arretxe, PhD Cristina Alonso, PhD Ekaterina Zhuravleva, PhD Raul Jimenez-Agüero, MD, PhD Emma Eizaguirre, MD, PhD María Jesús Pareja, MD, PhD Manuel Romero-Gómez, MD, PhD Marco Arrese Jimenez, MD, PhD Malte P. Suppli, MD, PhD Filip K. Knop, MD, PhD Stine Karlsen Oversoe, MD, PhD Gerda Elisabeth Villadsen, MD, PhD Thomas Decaens, MD, PhD Flair Jose Carrilho, MD, PhD Claudia PMS de Oliveira, MD, PhD Bruno Sangro, MD, PhD Rocio I.R. Macias, MD, PhD Jesus M. Banales, PhD Jesper B. Andersen, PhD |
| author_sort | Monika Lewinska, PhD |
| collection | DOAJ |
| description | Background: Non-alcoholic fatty liver disease (NAFLD) is affecting more people globally. Indeed, NAFLD is a spectrum of metabolic dysfunctions that can progress to hepatocellular carcinoma (NAFLD-HCC). This development can occur in a non-cirrhotic liver and thus, often lack clinical surveillance. The aim of this study was to develop non-invasive surveillance method for NAFLD-HCC. Methods: Using comprehensive ultra-high-performance liquid chromatography mass-spectrometry, we investigated 1,295 metabolites in serum from 249 patients. Area under the receiver operating characteristic curve was calculated for all detected metabolites and used to establish their diagnostic potential. Logistic regression analysis was used to establish the diagnostic score. Findings: We show that NAFLD-HCC is characterised by a complete rearrangement of the serum lipidome, which distinguishes NAFLD-HCC from non-cancerous individuals and other HCC patients. We used machine learning to build a diagnostic model for NAFLD-HCC. We quantified predictive metabolites and developed the NAFLD-HCC Diagnostic Score (NHDS), presenting superior diagnostic potential compared to alpha-fetoprotein (AFP). Patients’ metabolic landscapes show a progressive depletion in unsaturated fatty acids and acylcarnitines during transformation. Upregulation of fatty acid transporters in NAFLD-HCC tumours contribute to fatty acid depletion in the serum. Interpretation: NAFLD-HCC patients can be efficiently distinguished by serum metabolic alterations from the healthy population and from HCC patients related to other aetiologies (alcohol and viral hepatitis). Our model can be used for non-invasive surveillance of individuals with metabolic syndrome(s), allowing for early detection of NAFLD-HCC. Therefore, serum metabolomics may provide valuable insight to monitor patients at risk, including morbidly obese, diabetics, and NAFLD patients. Funding: The funding sources for this study had no role in study design, data collection, data analyses, interpretation or writing of the report as it is presented herein. |
| first_indexed | 2024-12-19T00:16:25Z |
| format | Article |
| id | doaj.art-a98663c5714b4b39a2da1a493b1539b3 |
| institution | Directory Open Access Journal |
| issn | 2352-3964 |
| language | English |
| last_indexed | 2024-12-19T00:16:25Z |
| publishDate | 2021-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EBioMedicine |
| spelling | doaj.art-a98663c5714b4b39a2da1a493b1539b32022-12-21T20:45:47ZengElsevierEBioMedicine2352-39642021-11-0173103661The altered serum lipidome and its diagnostic potential for Non-Alcoholic Fatty Liver (NAFL)-associated hepatocellular carcinomaMonika Lewinska, PhD0Alvaro Santos-Laso, PhD1Enara Arretxe, PhD2Cristina Alonso, PhD3Ekaterina Zhuravleva, PhD4Raul Jimenez-Agüero, MD, PhD5Emma Eizaguirre, MD, PhD6María Jesús Pareja, MD, PhD7Manuel Romero-Gómez, MD, PhD8Marco Arrese Jimenez, MD, PhD9Malte P. Suppli, MD, PhD10Filip K. Knop, MD, PhD11Stine Karlsen Oversoe, MD, PhD12Gerda Elisabeth Villadsen, MD, PhD13Thomas Decaens, MD, PhD14Flair Jose Carrilho, MD, PhD15Claudia PMS de Oliveira, MD, PhD16Bruno Sangro, MD, PhD17Rocio I.R. Macias, MD, PhD18Jesus M. Banales, PhD19Jesper B. Andersen, PhD20Biotech Research and Innovation Centre, Department of Health and Medical Sciences, University of Copenhagen, DenmarkDepartment of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute - Donostia University Hospital, University of the Basque Country (UPV/EHU), San Sebastian, SpainOWL Metabolomics, Derio, SpainOWL Metabolomics, Derio, SpainBiotech Research and Innovation Centre, Department of Health and Medical Sciences, University of Copenhagen, DenmarkDepartment of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute - Donostia University Hospital, University of the Basque Country (UPV/EHU), San Sebastian, SpainDepartment of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute - Donostia University Hospital, University of the Basque Country (UPV/EHU), San Sebastian, SpainHospital Juan Ramón Jiménez - Huelva, SpainUCM Digestive Diseases. Virgen del Rocío University Hospital. SeLiver group at the Institute of Biomedicine of Seville (IBIS). The University of Seville. Sevilla, Spain; Center for the Study of Liver and Gastrointestinal Diseases (CIBERehd), Carlos III National Institute of Health, Madrid, SpainDepartment of Gastroenterology, Escuela de Medicina, Centro de Envejecimiento y Regeneración (CARE), Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, ChileCenter for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, DenmarkCenter for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark; Steno Diabetes Center Copenhagen, Gentofte, DenmarkDepartment of Hepatology and Gastroenterology, Aarhus University Hospital, DenmarkDepartment of Hepatology and Gastroenterology, Aarhus University Hospital, DenmarkUniversité Grenoble Alpes, Grenoble, France; Department of Hepatology and Gastroenterology, CHU-Grenoble Alpes, FranceDepartment of Gastroenterology, Faculdade de Medicina da Universidade de São Paulo, BrazilDepartment of Gastroenterology, Faculdade de Medicina da Universidade de São Paulo, BrazilCenter for the Study of Liver and Gastrointestinal Diseases (CIBERehd), Carlos III National Institute of Health, Madrid, Spain; Liver Unit, Clinica Universidad de Navarra-IDISNA and CIBEREHD, Pamplona, SpainCenter for the Study of Liver and Gastrointestinal Diseases (CIBERehd), Carlos III National Institute of Health, Madrid, Spain; Experimental Hepatology and Drug Targeting (HEVEPHARM) group, IBSAL, University of Salamanca, Salamanca, SpainDepartment of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute - Donostia University Hospital, University of the Basque Country (UPV/EHU), San Sebastian, Spain; Center for the Study of Liver and Gastrointestinal Diseases (CIBERehd), Carlos III National Institute of Health, Madrid, Spain; IKERBASQUE, Basque Foundation for Science, Bilbao, SpainBiotech Research and Innovation Centre, Department of Health and Medical Sciences, University of Copenhagen, Denmark; Corresponding author: Jesper B Andersen, Ole Maaløes Vej 5, Copenhagen N, DK-2200 Denmark. Phone: +45 35325834, FAX: +45 72620285Background: Non-alcoholic fatty liver disease (NAFLD) is affecting more people globally. Indeed, NAFLD is a spectrum of metabolic dysfunctions that can progress to hepatocellular carcinoma (NAFLD-HCC). This development can occur in a non-cirrhotic liver and thus, often lack clinical surveillance. The aim of this study was to develop non-invasive surveillance method for NAFLD-HCC. Methods: Using comprehensive ultra-high-performance liquid chromatography mass-spectrometry, we investigated 1,295 metabolites in serum from 249 patients. Area under the receiver operating characteristic curve was calculated for all detected metabolites and used to establish their diagnostic potential. Logistic regression analysis was used to establish the diagnostic score. Findings: We show that NAFLD-HCC is characterised by a complete rearrangement of the serum lipidome, which distinguishes NAFLD-HCC from non-cancerous individuals and other HCC patients. We used machine learning to build a diagnostic model for NAFLD-HCC. We quantified predictive metabolites and developed the NAFLD-HCC Diagnostic Score (NHDS), presenting superior diagnostic potential compared to alpha-fetoprotein (AFP). Patients’ metabolic landscapes show a progressive depletion in unsaturated fatty acids and acylcarnitines during transformation. Upregulation of fatty acid transporters in NAFLD-HCC tumours contribute to fatty acid depletion in the serum. Interpretation: NAFLD-HCC patients can be efficiently distinguished by serum metabolic alterations from the healthy population and from HCC patients related to other aetiologies (alcohol and viral hepatitis). Our model can be used for non-invasive surveillance of individuals with metabolic syndrome(s), allowing for early detection of NAFLD-HCC. Therefore, serum metabolomics may provide valuable insight to monitor patients at risk, including morbidly obese, diabetics, and NAFLD patients. Funding: The funding sources for this study had no role in study design, data collection, data analyses, interpretation or writing of the report as it is presented herein.http://www.sciencedirect.com/science/article/pii/S2352396421004552NAFLDHCCmetabolomicslipidomicsbiomarker discovery |
| spellingShingle | Monika Lewinska, PhD Alvaro Santos-Laso, PhD Enara Arretxe, PhD Cristina Alonso, PhD Ekaterina Zhuravleva, PhD Raul Jimenez-Agüero, MD, PhD Emma Eizaguirre, MD, PhD María Jesús Pareja, MD, PhD Manuel Romero-Gómez, MD, PhD Marco Arrese Jimenez, MD, PhD Malte P. Suppli, MD, PhD Filip K. Knop, MD, PhD Stine Karlsen Oversoe, MD, PhD Gerda Elisabeth Villadsen, MD, PhD Thomas Decaens, MD, PhD Flair Jose Carrilho, MD, PhD Claudia PMS de Oliveira, MD, PhD Bruno Sangro, MD, PhD Rocio I.R. Macias, MD, PhD Jesus M. Banales, PhD Jesper B. Andersen, PhD The altered serum lipidome and its diagnostic potential for Non-Alcoholic Fatty Liver (NAFL)-associated hepatocellular carcinoma EBioMedicine NAFLD HCC metabolomics lipidomics biomarker discovery |
| title | The altered serum lipidome and its diagnostic potential for Non-Alcoholic Fatty Liver (NAFL)-associated hepatocellular carcinoma |
| title_full | The altered serum lipidome and its diagnostic potential for Non-Alcoholic Fatty Liver (NAFL)-associated hepatocellular carcinoma |
| title_fullStr | The altered serum lipidome and its diagnostic potential for Non-Alcoholic Fatty Liver (NAFL)-associated hepatocellular carcinoma |
| title_full_unstemmed | The altered serum lipidome and its diagnostic potential for Non-Alcoholic Fatty Liver (NAFL)-associated hepatocellular carcinoma |
| title_short | The altered serum lipidome and its diagnostic potential for Non-Alcoholic Fatty Liver (NAFL)-associated hepatocellular carcinoma |
| title_sort | altered serum lipidome and its diagnostic potential for non alcoholic fatty liver nafl associated hepatocellular carcinoma |
| topic | NAFLD HCC metabolomics lipidomics biomarker discovery |
| url | http://www.sciencedirect.com/science/article/pii/S2352396421004552 |
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