Bioinformatics based analysis of key genes underlying the development of nonalcoholic fatty liver disease / 中华内分泌代谢杂志

ABSTRACT

Objective:To identify key genes and their potential biological mechanisms in the progression of non-alcoholic fatty liver disease (NAFLD) using bioinformatics technology.Methods:Genes differentially expressed in simple non-alcoholic fatty liver disease (NAFL) and non-alcoholic steatohepatitis (NASH) were analyzed by integrating NAFLD-related sequencing datasets GSE135251 and GSE167523 from the Gene Expression Omnibus (GEO) datebase. Gene Ontology (GO) functional enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) and Reactome signaling pathway analysis were performed. Key genes were identified by STRING database and Cytoscape3.7.2 software, and the expression of key genes under different fibrosis grades and activity scores was observed. In addition, the expression of key genes in different cell clusters was observed based on the single-cell RNA-seq dataset of NAFLD mice.Results:Bioinformatics methods were used to obtain 97 common differential genes in NAFLD from two datasets. GO functional enrichment analysis was mainly performed in Extracellular Matrix (ECM) tissues. The main signaling pathway is ECM-receptor interaction. Five key genes were identified based on PPI network and Cytoscape software COL1A1, THBS2, CXCL8, THY1 and LOXL1. The expression of key genes was significantly positively correlated with fibrosis grade and activity score, indicating that they were closely related to the progression of NAFLD. These key genes are highly expressed in hepatic stellate cells (HSCs) and natural killer/T cells (NK/T cells).Conclusion:In this study, bioinformatics technology was used to identify five key genes that may be involved in the NAFL-NASH transformation, suggesting that the ECM-receptor interaction signaling pathway may be a key molecular mechanism of NAFLD disease progression.