Integrated Multichip Analysis Identifies Potential Key Genes in the Pathogenesis of Nonalcoholic Steatohepatitis

作者：Jianzhong Ye, Yishuai Lin, Qīng Wáng, Yating Li, Yajie Zhao, Lijiang Chen, Qing Wu, Chunquan Xu, Cui Zhou, Yao Sun, Wanchun Ye, Fumao Bai, Tieli Zhou · 发表于：Frontiers in Endocrinology · 年份：2020 · DOI：10.3389/fendo.2020.601745 · 被引用次数：14 · 研究领域：Liver Disease Diagnosis and Treatment、Liver Diseases and Immunity、Adipokines, Inflammation, and Metabolic Diseases

Background Nonalcoholic steatohepatitis (NASH) is rapidly becoming a major chronic liver disease worldwide. However, little is known concerning the pathogenesis and progression mechanism of NASH. Our aim here is to identify key genes and elucidate their biological function in the progression from hepatic steatosis to NASH. Methods Gene expression datasets containing NASH patients, hepatic steatosis patients, and healthy subjects were downloaded from the Gene Expression Omnibus database, using the R packages biobase and GEOquery. Differentially expressed genes (DEGs) were identified using the R limma package. Functional annotation and enrichment analysis of DEGs were undertaken using the R package ClusterProfile. Protein-protein interaction (PPI) networks were constructed using the STRING database. Results Three microarray datasets GSE48452, GSE63067 and GSE89632 were selected. They included 45 NASH patients, 31 hepatic steatosis patients, and 43 healthy subjects. Two up-regulated and 24 down-regulated DEGs were found in both NASH patients vs. healthy controls and in steatosis subjects vs. healthy controls. The most significantly differentially expressed genes were FOSB ( P = 3.43×10 -15 ), followed by CYP7A1 ( P = 2.87×10 -11 ), and FOS ( P = 6.26×10 -11 ). Proximal promoter DNA-binding transcription activator activity, RNA polymerase II-specific ( P = 1.30×10 -5 ) was the most significantly enriched functional term in the gene ontology analysis. KEGG pathway enrichment analy...