FABP4 and MMP9 levels identified as predictive factors for poor prognosis in patients with nonalcoholic fatty liver using data mining approaches and gene expression analysis

Nonalcoholic fatty liver (NAFLD) may progress to nonalcoholic steatohepatitis (NASH) and ultimately to cirrhosis and hepatocellular carcinoma (HCC). Prognostic markers for these conditions are poorly defined. The aim of this study was to identify predictive gene markers for the transition from NAFL...

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Published in:Scientific reports Vol. 9; no. 1; pp. 19785 - 16
Main Authors: Coilly, Audrey, Desterke, Christophe, Guettier, Catherine, Samuel, Didier, Chiappini, Franck
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 24.12.2019
Nature Publishing Group
Subjects:
38/39
45
45/61
631/114/2407
692/4020/4021
Adult
Aged
Cirrhosis
Data Mining
Databases, Nucleic Acid
Fatty acid-binding protein
Fatty Acid-Binding Proteins - biosynthesis
Fatty liver
Female
Food and Nutrition
Gelatinase B
Gene expression
Gene Expression Profiling
Gene Expression Regulation
Hepatocellular carcinoma
Humanities and Social Sciences
Humans
Life Sciences
Liver cancer
Liver cirrhosis
Male
Matrix metalloproteinase
Matrix Metalloproteinase 9 - biosynthesis
Metalloproteinase
Middle Aged
multidisciplinary
Non-alcoholic Fatty Liver Disease - diagnosis
Non-alcoholic Fatty Liver Disease - metabolism
Non-alcoholic Fatty Liver Disease - pathology
Oligonucleotide Array Sequence Analysis
Predictive Value of Tests
Prognosis
Science
Science (multidisciplinary)
Steatosis
Hepatology, Microarrays
ISSN:2045-2322, 2045-2322
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Abstract Nonalcoholic fatty liver (NAFLD) may progress to nonalcoholic steatohepatitis (NASH) and ultimately to cirrhosis and hepatocellular carcinoma (HCC). Prognostic markers for these conditions are poorly defined. The aim of this study was to identify predictive gene markers for the transition from NAFL to NASH and then to poorer conditions. Gene expression omnibus datasets associated with a prediction analysis algorithm were used to create a matrix composed of control subject (n = 52), healthy obese (n = 51), obese with NAFL (n = 42) and NASH patients (n = 37) and 19,085 genes in order to identify specific genes predictive of the transition from steatosis to NASH and from NASH to cirrhosis and HCC and thus patients at high risk of complications. A validation cohort was used to validate these results. We identified two genes, fatty acid binding protein-4 (FABP4) and matrix metalloproteinase-9 (MMP9), which respectively allowed distinguishing patients at risk of progression from NAFL to NASH and from NASH to cirrhosis and HCC. Thus, NAFL patients expressing high hepatic levels of FABP4 and NASH patients expressing high hepatic levels of MMP9 are likely to experience disease progression. Therefore, using FABP4 and MMP9 as blood markers could help to predict poor outcomes and/or progression of NAFL during clinical trial follow-up.
AbstractList Nonalcoholic fatty liver (NAFLD) may progress to nonalcoholic steatohepatitis (NASH) and ultimately to cirrhosis and hepatocellular carcinoma (HCC). Prognostic markers for these conditions are poorly defined. The aim of this study was to identify predictive gene markers for the transition from NAFL to NASH and then to poorer conditions. Gene expression omnibus datasets associated with a prediction analysis algorithm were used to create a matrix composed of control subject (n = 52), healthy obese (n = 51), obese with NAFL (n = 42) and NASH patients (n = 37) and 19,085 genes in order to identify specific genes predictive of the transition from steatosis to NASH and from NASH to cirrhosis and HCC and thus patients at high risk of complications. A validation cohort was used to validate these results. We identified two genes, fatty acid binding protein-4 (FABP4) and matrix metalloproteinase-9 (MMP9), which respectively allowed distinguishing patients at risk of progression from NAFL to NASH and from NASH to cirrhosis and HCC. Thus, NAFL patients expressing high hepatic levels of FABP4 and NASH patients expressing high hepatic levels of MMP9 are likely to experience disease progression. Therefore, using FABP4 and MMP9 as blood markers could help to predict poor outcomes and/or progression of NAFL during clinical trial follow-up.
Nonalcoholic fatty liver (NAFLD) may progress to nonalcoholic steatohepatitis (NASH) and ultimately to cirrhosis and hepatocellular carcinoma (HCC). Prognostic markers for these conditions are poorly defined. The aim of this study was to identify predictive gene markers for the transition from NAFL to NASH and then to poorer conditions. Gene expression omnibus datasets associated with a prediction analysis algorithm were used to create a matrix composed of control subject (n = 52), healthy obese (n = 51), obese with NAFL (n = 42) and NASH patients (n = 37) and 19,085 genes in order to identify specific genes predictive of the transition from steatosis to NASH and from NASH to cirrhosis and HCC and thus patients at high risk of complications. A validation cohort was used to validate these results. We identified two genes, fatty acid binding protein-4 (FABP4) and matrix metalloproteinase-9 (MMP9), which respectively allowed distinguishing patients at risk of progression from NAFL to NASH and from NASH to cirrhosis and HCC. Thus, NAFL patients expressing high hepatic levels of FABP4 and NASH patients expressing high hepatic levels of MMP9 are likely to experience disease progression. Therefore, using FABP4 and MMP9 as blood markers could help to predict poor outcomes and/or progression of NAFL during clinical trial follow-up.Nonalcoholic fatty liver (NAFLD) may progress to nonalcoholic steatohepatitis (NASH) and ultimately to cirrhosis and hepatocellular carcinoma (HCC). Prognostic markers for these conditions are poorly defined. The aim of this study was to identify predictive gene markers for the transition from NAFL to NASH and then to poorer conditions. Gene expression omnibus datasets associated with a prediction analysis algorithm were used to create a matrix composed of control subject (n = 52), healthy obese (n = 51), obese with NAFL (n = 42) and NASH patients (n = 37) and 19,085 genes in order to identify specific genes predictive of the transition from steatosis to NASH and from NASH to cirrhosis and HCC and thus patients at high risk of complications. A validation cohort was used to validate these results. We identified two genes, fatty acid binding protein-4 (FABP4) and matrix metalloproteinase-9 (MMP9), which respectively allowed distinguishing patients at risk of progression from NAFL to NASH and from NASH to cirrhosis and HCC. Thus, NAFL patients expressing high hepatic levels of FABP4 and NASH patients expressing high hepatic levels of MMP9 are likely to experience disease progression. Therefore, using FABP4 and MMP9 as blood markers could help to predict poor outcomes and/or progression of NAFL during clinical trial follow-up.
ArticleNumber 19785
Author Coilly, Audrey
Desterke, Christophe
Samuel, Didier
Guettier, Catherine
Chiappini, Franck
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  givenname: Audrey
  surname: Coilly
  fullname: Coilly, Audrey
  organization: Inserm, UMR-U1193, Univ Paris-Sud, Institut André Lwoff, DHU Hepatinov, AP-HP, Centre Hépatobiliaire, Hôpital Paul Brousse
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  givenname: Christophe
  surname: Desterke
  fullname: Desterke, Christophe
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  givenname: Catherine
  surname: Guettier
  fullname: Guettier, Catherine
  organization: Inserm, UMR-U1193, Univ Paris-Sud, Institut André Lwoff, DHU Hepatinov, AP-HP, Service d’Anatomopathologie, Hôpital Bicêtre
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  givenname: Didier
  surname: Samuel
  fullname: Samuel, Didier
  organization: Inserm, UMR-U1193, Univ Paris-Sud, Institut André Lwoff, DHU Hepatinov, AP-HP, Centre Hépatobiliaire, Hôpital Paul Brousse
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  surname: Chiappini
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  email: fchiappini@yahoo.fr
  organization: Inserm, UMR-U1193, Univ Paris-Sud, Institut André Lwoff, DHU Hepatinov, Laboratoire Croissance, Régénération, Réparation et Régénération Tissulaires (CRRET)/EAC CNRS 7149, Univ Paris-Est Créteil (UPEC)
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https://hal.science/hal-05043454$$DView record in HAL
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Issue 1
Keywords Hepatology, Microarrays
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Snippet Nonalcoholic fatty liver (NAFLD) may progress to nonalcoholic steatohepatitis (NASH) and ultimately to cirrhosis and hepatocellular carcinoma (HCC). Prognostic...
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Enrichment Source
Publisher
StartPage 19785
SubjectTerms 38/39
45
45/61
631/114/2407
692/4020/4021
Adult
Aged
Cirrhosis
Data Mining
Databases, Nucleic Acid
Fatty acid-binding protein
Fatty Acid-Binding Proteins - biosynthesis
Fatty liver
Female
Food and Nutrition
Gelatinase B
Gene expression
Gene Expression Profiling
Gene Expression Regulation
Hepatocellular carcinoma
Humanities and Social Sciences
Humans
Life Sciences
Liver cancer
Liver cirrhosis
Male
Matrix metalloproteinase
Matrix Metalloproteinase 9 - biosynthesis
Metalloproteinase
Middle Aged
multidisciplinary
Non-alcoholic Fatty Liver Disease - diagnosis
Non-alcoholic Fatty Liver Disease - metabolism
Non-alcoholic Fatty Liver Disease - pathology
Oligonucleotide Array Sequence Analysis
Predictive Value of Tests
Prognosis
Science
Science (multidisciplinary)
Steatosis
Title FABP4 and MMP9 levels identified as predictive factors for poor prognosis in patients with nonalcoholic fatty liver using data mining approaches and gene expression analysis
URI https://link.springer.com/article/10.1038/s41598-019-56235-y
https://www.ncbi.nlm.nih.gov/pubmed/31874999
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https://www.proquest.com/docview/2330598553
https://hal.science/hal-05043454
https://pubmed.ncbi.nlm.nih.gov/PMC6930227
Volume 9
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