AUTHOR=Meng Qingnan , Li Xiaoying , Xiong Xuelian 

TITLE=Identification of Hub Genes Associated With Non-alcoholic Steatohepatitis Using Integrated Bioinformatics Analysis

JOURNAL=Frontiers in Genetics

VOLUME=Volume 13 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2022.872518

DOI=10.3389/fgene.2022.872518

ISSN=1664-8021

ABSTRACT=Background & aims: The most prevalent liver condition, non-alcoholic fatty liver disease (NAFLD), is comprised of non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH). Due to its epidemiology and poor prognosis, it is critical to understand the mechanisms underlying NASH. However, the etiology and progression mechanisms of NASH remain largely unknown. In addition, the gold standard for 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 differentially expressed gene (DEG) analysis in order to investigate the association between gene sets and clinical features, as well as to uncover co-expression modules. A protein-protein interaction (PPI) network was created to extract hub genes. The results were confirmed using another publicly available dataset and mice treated with high-fat diet (HFD) and carbon tetrachloride (CCl4).
Results: A total of 24 differentially co-expressed genes were selected by WGCNA and DEG 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, 3 of the 8 genes were validated in both a public dataset and a mouse model.
Conclusion: Our research discovered genes that have the potential to mediate the process NASH and might be useful diagnostic biomarkers for the disorder.