Gene expression profiling reveals key genes and pathways related to the development of non-alcoholic fatty liver disease
Journal Title: Annals of Hepatology - Year 2016, Vol 15, Issue 2
Abstract
Background. This study aims to identify key genes and pathways involved in non-alcoholic fatty liver disease (NAFLD). Materialand methods. The dataset GSE48452 was downloaded from Gene Expression Omnibus, including 14 control liver samples, 27healthy obese samples, 14 steatosis samples and 18 nonalcoholic steatohepatitis (NASH) samples. Differentially expressed genes(DEGs) between controls and other samples were screened through LIMMA package. Then pathway enrichment analysis for DEGs was performed by using DAVID, and alterations of enriched pathways were determined. Furthermore, protein-protein interaction (PPI) networks were constructed based on the PPI information from HPRD database, and then, networks were visualized through Cytoscape. Additionally, interactions between microRNAs (miRNAs) and pathways were analyzed via Fisher’s exact test. Results. A total of 505, 814 and 783 DEGs were identified for healthy obese, steatosis and NASH samples in comparison with controls, respectively. DEGs were enriched in ribosome (RPL36A, RPL14, etc.), ubiquitin mediated proteolysis (UBE2A, UBA7, etc.), focal adhesion (PRKCA, EGFR, CDC42, VEGFA, etc.), Fc?R-mediated phagocytosis (PRKCA, CDC42, etc.), and so on. The 27 enriched pathways gradually deviated from baseline (namely, controls) along with the changes of obese-steatosis-NASH. In PPI networks, PRKCA interacted with EGFR and CDC42. Besides, hsa-miR-330-3p and hsa-miR-126 modulated focal adhesion through targeting VEGFA and CDC42. Conclusions. The identified DEGs (PRKCA, EGFR, CDC42, VEGFA), disturbed pathways (ribosome, ubiquitin mediated proteolysis, focal adhesion, Fc?R-mediated phagocytosis, etc.) and miRNAs (hsa-miR-330-3p, hsa-miR-126, etc.) might be closely related to NAFLD progression. These results might contribute to understanding NAFLD mechanism, conducting experimentalresearches, and designing clinical practices.
Authors and Affiliations
Ruifeng Wang, Xiaobing Wang, Liwei Zhuang
Keywords
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