Abstract
BackgroundNonalcoholic 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.MethodsGene 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.ResultsThree 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 analysis indicated that the MAPK signaling pathway (P = 3.11×10-4) was significantly enriched.ConclusionThis study characterized hub genes of the liver transcriptome, which may contribute functionally to NASH progression from hepatic steatosis.
Highlights
Nonalcoholic steatohepatitis (NASH) is a severe form of nonalcoholic fatty liver disease (NAFLD)
Two up-regulated and 24 down-regulated differentially expressed genes (DEGs) were found in both NASH patients vs. healthy controls and in steatosis subjects vs. healthy controls
Datasets meeting the following criteria were excluded from the study: 1) patients with other diseases, such as hepatocellular carcinoma (HCC); 2) obese subjects matched as controls; 3) ambiguous diagnosis, as such where steatosis and NASH were collectively referred to as NAFLD
Summary
Nonalcoholic steatohepatitis (NASH) is a severe form of nonalcoholic fatty liver disease (NAFLD). The global prevalence of NASH is approximately 1.5%–6.5% [1]. Patients with NASH, especially those with advanced fibrosis, are more likely to progress to hepatocellular carcinoma (HCC) [2]. It has been suggested that NASH will become the principal indication for liver transplantation in the near future [3]. NASH is a major public health concern due to its increasing prevalence and poor prognosis [4]. Nonalcoholic steatohepatitis (NASH) is rapidly becoming a major chronic liver disease worldwide. Little is known concerning the pathogenesis and progression mechanism of NASH.
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