AUTHOR=Ye Jianzhong , Lin Yishuai , Wang Qing , Li Yating , Zhao Yajie , Chen Lijiang , Wu Qing , Xu Chunquan , Zhou Cui , Sun Yao , Ye Wanchun , Bai Fumao , Zhou Tieli 

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

JOURNAL=Frontiers in Endocrinology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2020.601745

DOI=10.3389/fendo.2020.601745

ISSN=1664-2392

ABSTRACT=<sec><title>Background</title><p>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.</p></sec><sec><title>Methods</title><p>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.</p></sec><sec><title>Results</title><p>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 <italic>FOSB</italic> (<italic>P</italic> = 3.43×10<sup>-15</sup>), followed by <italic>CYP7A1</italic> (<italic>P</italic> = 2.87×10<sup>-11</sup>), and <italic>FOS</italic> (<italic>P</italic> = 6.26×10<sup>-11</sup>). Proximal promoter DNA-binding transcription activator activity, RNA polymerase II-specific (<italic>P</italic> = 1.30×10<sup>-5</sup>) was the most significantly enriched functional term in the gene ontology analysis. KEGG pathway enrichment analysis indicated that the MAPK signaling pathway (<italic>P</italic> = 3.11×10<sup>-4</sup>) was significantly enriched.</p></sec><sec><title>Conclusion</title><p>This study characterized hub genes of the liver transcriptome, which may contribute functionally to NASH progression from hepatic steatosis.</p></sec>