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Identification of Hub Genes Associated With Non-alcoholic Steatohepatitis Using Integrated Bioinformatics Analysis
Background and aims: As a major cause of liver disease worldwide, non-alcoholic fatty liver disease (NAFLD) comprises non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH). Due to the high prevalence and poor prognosis of NASH, it is critical to understand its mechanisms. However...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9086399/ https://www.ncbi.nlm.nih.gov/pubmed/35559030 http://dx.doi.org/10.3389/fgene.2022.872518 |
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author | Meng, Qingnan Li, Xiaoying Xiong, Xuelian |
author_facet | Meng, Qingnan Li, Xiaoying Xiong, Xuelian |
author_sort | Meng, Qingnan |
collection | PubMed |
description | Background and aims: As a major cause of liver disease worldwide, non-alcoholic fatty liver disease (NAFLD) comprises non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH). Due to the high prevalence and poor prognosis of NASH, it is critical to understand its mechanisms. However, the etiology and mechanisms remain largely unknown. In addition, the gold standard for the diagnosis of NASH is liver biopsy, which is an invasive procedure. Therefore, there is a pressing need to develop noninvasive tests for NASH diagnosis. The goal of the study is to discover key genes involved in NASH development and investigate their value as noninvasive biomarkers. Methods: The Gene Expression Omnibus (GEO) database was used to obtain two datasets encompassing NASH patients and healthy controls. We used weighted gene co-expression network analysis (WGCNA) and differential expression analysis in order to investigate the association between gene sets and clinical features, as well as to discover co-expression modules. A protein-protein interaction (PPI) network was created to extract hub genes. The results were validated using another publicly available dataset and mice treated with a high-fat diet (HFD) and carbon tetrachloride (CCl4). Results: A total of 24 differentially co-expressed genes were selected by WGCNA and differential expression analysis. KEGG analysis indicated most of them were enriched in the focal adhesion pathway. GO analysis showed these genes were mainly enriched in circadian rhythm, aging, angiogenesis and response to drug (biological process), endoplasmic reticulum lumen (cellular component), and protein binding (molecular function). As a result, eight genes (JUN, SERPINE1, GINS2, TYMS, HMMR, IGFBP2, BIRC3, TNFRSF12A) were identified as hub genes. Finally, three genes were found significantly changed in both the validation dataset and the mouse model. Conclusion: Our research discovered genes that have the potential to mediate the process of NASH and might be useful diagnostic biomarkers for the disorder. |
format | Online Article Text |
id | pubmed-9086399 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-90863992022-05-11 Identification of Hub Genes Associated With Non-alcoholic Steatohepatitis Using Integrated Bioinformatics Analysis Meng, Qingnan Li, Xiaoying Xiong, Xuelian Front Genet Genetics Background and aims: As a major cause of liver disease worldwide, non-alcoholic fatty liver disease (NAFLD) comprises non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH). Due to the high prevalence and poor prognosis of NASH, it is critical to understand its mechanisms. However, the etiology and mechanisms remain largely unknown. In addition, the gold standard for the diagnosis of NASH is liver biopsy, which is an invasive procedure. Therefore, there is a pressing need to develop noninvasive tests for NASH diagnosis. The goal of the study is to discover key genes involved in NASH development and investigate their value as noninvasive biomarkers. Methods: The Gene Expression Omnibus (GEO) database was used to obtain two datasets encompassing NASH patients and healthy controls. We used weighted gene co-expression network analysis (WGCNA) and differential expression analysis in order to investigate the association between gene sets and clinical features, as well as to discover co-expression modules. A protein-protein interaction (PPI) network was created to extract hub genes. The results were validated using another publicly available dataset and mice treated with a high-fat diet (HFD) and carbon tetrachloride (CCl4). Results: A total of 24 differentially co-expressed genes were selected by WGCNA and differential expression analysis. KEGG analysis indicated most of them were enriched in the focal adhesion pathway. GO analysis showed these genes were mainly enriched in circadian rhythm, aging, angiogenesis and response to drug (biological process), endoplasmic reticulum lumen (cellular component), and protein binding (molecular function). As a result, eight genes (JUN, SERPINE1, GINS2, TYMS, HMMR, IGFBP2, BIRC3, TNFRSF12A) were identified as hub genes. Finally, three genes were found significantly changed in both the validation dataset and the mouse model. Conclusion: Our research discovered genes that have the potential to mediate the process of NASH and might be useful diagnostic biomarkers for the disorder. Frontiers Media S.A. 2022-04-26 /pmc/articles/PMC9086399/ /pubmed/35559030 http://dx.doi.org/10.3389/fgene.2022.872518 Text en Copyright © 2022 Meng, Li and Xiong. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Genetics Meng, Qingnan Li, Xiaoying Xiong, Xuelian Identification of Hub Genes Associated With Non-alcoholic Steatohepatitis Using Integrated Bioinformatics Analysis |
title | Identification of Hub Genes Associated With Non-alcoholic Steatohepatitis Using Integrated Bioinformatics Analysis |
title_full | Identification of Hub Genes Associated With Non-alcoholic Steatohepatitis Using Integrated Bioinformatics Analysis |
title_fullStr | Identification of Hub Genes Associated With Non-alcoholic Steatohepatitis Using Integrated Bioinformatics Analysis |
title_full_unstemmed | Identification of Hub Genes Associated With Non-alcoholic Steatohepatitis Using Integrated Bioinformatics Analysis |
title_short | Identification of Hub Genes Associated With Non-alcoholic Steatohepatitis Using Integrated Bioinformatics Analysis |
title_sort | identification of hub genes associated with non-alcoholic steatohepatitis using integrated bioinformatics analysis |
topic | Genetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9086399/ https://www.ncbi.nlm.nih.gov/pubmed/35559030 http://dx.doi.org/10.3389/fgene.2022.872518 |
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