Gerda Elisabeth Villadsen

The altered serum lipidome and its diagnostic potential for Non-Alcoholic Fatty Liver (NAFL)-associated hepatocellular carcinoma: Diagnosis of NAFLD-HCC utilising serum lipidomics

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

  • Monika Lewinska, University of Copenhagen
  • ,
  • Alvaro Santos-Laso, Instituto de Investigación Sanitaria Biodonostia
  • ,
  • Enara Arretxe, OWL Metabolomics
  • ,
  • Cristina Alonso, OWL Metabolomics
  • ,
  • Ekaterina Zhuravleva, University of Copenhagen
  • ,
  • Raul Jimenez-Agüero, Instituto de Investigación Sanitaria Biodonostia
  • ,
  • Emma Eizaguirre, Instituto de Investigación Sanitaria Biodonostia
  • ,
  • María Jesús Pareja, Hospital Universitario Juan Ramón Jiménez
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  • Manuel Romero-Gómez, University of Seville, CIBER - Center for Biomedical Research Network
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  • Marco Arrese Jimenez, Pontificia Universidad Catolica de Chile
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  • Malte P. Suppli, University of Copenhagen
  • ,
  • Filip K. Knop, University of Copenhagen, Steno Diabetes Centre
  • ,
  • Stine Karlsen Oversoe
  • Gerda Elisabeth Villadsen
  • Thomas Decaens, Universite Grenoble Alpes
  • ,
  • Flair Jose Carrilho, Universidade de Sao Paulo
  • ,
  • Claudia PMS de Oliveira, Universidade de Sao Paulo
  • ,
  • Bruno Sangro, CIBER - Center for Biomedical Research Network, University of Navarra
  • ,
  • Rocio I.R. Macias, CIBER - Center for Biomedical Research Network, Universidad de Salamanca
  • ,
  • Jesus M. Banales, Instituto de Investigación Sanitaria Biodonostia, CIBER - Center for Biomedical Research Network, Ikerbasque Basque Foundation for Science
  • ,
  • Jesper B. Andersen, Biotech Research and Innovation Centre, University of Copenhagen

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.

Original languageEnglish
Article number103661
JournalEBioMedicine
Volume73
DOIs
Publication statusPublished - Nov 2021

Bibliographical note

Publisher Copyright:
© 2021 The Author(s)

    Research areas

  • biomarker discovery, HCC, lipidomics, metabolomics, NAFLD

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