Artículo
The altered serum lipidome and its diagnostic potential for Non-Alcoholic Fatty Liver (NAFL)-associated hepatocellular carcinoma
Autor/es | Lewinska, Monika
Santos-Laso, Álvaro Arretxe, Enara Alonso, Cristina Zhuravleva, Ekaterina Jiménez-Agüero, Raúl Romero Gómez, Manuel Andersen, Jesper B. |
Departamento | Universidad de Sevilla. Departamento de Medicina |
Fecha de publicación | 2021-12 |
Fecha de depósito | 2022-11-14 |
Publicado en |
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Resumen | 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 ... 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. |
Agencias financiadoras | Instituto de Salud Carlos III PI18/01075; CON14/00129; CPII19/00008 Fundación científica de la Acociación Española Contra el Cáncer BIOEF BIO15/CA/016/BD CIBERehd Comision Nacional de Investigacion, Ciencia y Tecnologia (CONICYT) AFB170005 Danish Cancer Society R98-A6446; R167A10784; R278-A16638 Danish Medical Research Council 4183-00118A; 1030-00070B Departamento de Salud del País Vasco 2017111010 European Commission Horizon 2020 program (ESCALON project) 825510 Euskadi RIS3 2019222054; 2020333010 Fondo Nacional De Ciencia y Tecnologia de Chile (FONDECYT) 1191145 Departamento de Industria del País Vasco KK-2020/000 08 IKERBASQUE, Fundación vasca por la Ciencia, España Novo Nordisk Foundation 14040; 0058419 Ministerio de Economía y Competitividad de España |
Identificador del proyecto | PI18/01075
CON14/00129 CPII19/00008 BIO15/CA/016/BD AFB170005 R98-A6446 R167A10784 R278-A16638 4183-00118A 1030-00070B 2017111010 KK-2020/000 08 825510 2019222054 2020333010 1191145 14040 0058419 |
Cita | Lewinska, M., Santos-Laso, Á., Arretxe, E., Alonso, C., Zhuravleva, E., Jiménez-Agüero, R.,...,Andersen, J.B. (2021). The altered serum lipidome and its diagnostic potential for Non-Alcoholic Fatty Liver (NAFL)-associated hepatocellular carcinoma. EBioMedicine, 73, 103661. https://doi.org/10.1016/j.ebiom.2021.103661. |
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