Prediction of crucial epigenetically-associated, differentially expressed genes by integrated bioinformatics analysis and the identification of S100A9 as a novel biomarker in psoriasis

Abstract

Psoriasis is one of the most common immune-mediated inflammatory diseases of the skin. The identification of the pivotal molecular mechanisms responsible for the disease pathogenesis may lead to the development of novel therapeutic options. The present study aimed to identify pivotal differentially expressed genes (DEGs) and methylated DEGs in psoriasis. The raw data from gene microarrays were obtained from the Gene Expression Omnibus database. The data were processed using packages in Bioconductor. In total, 352 upregulated and 137 downregulated DEGs were identified. The upregulated DEGs were primarily enriched in the 'innate immune defense' response and the 'cell cycle'. The down-regulated DEGs were primarily enriched in 'cell adhesion' and 'tight junction pathways'. A total of 95 methylated DEGs were identified, which were significantly enriched in the 'interleukin (IL)-17 signaling pathway' and the 'response to interferon'. Based on a comprehensive evaluation of all algorithms in cytoHubba, the key epigenetic-associated hub genes (S100A9, SELL, FCGR3B, MMP9, S100A7, IL7R, IRF7, CCR7, IFI44, CXCL1 and LCN2) were screened out. In order to further validate these genes, the present study constructed a model of imiquimod (IMQ)-induced psoriasiform dermatitis using mice. The levels of these hub genes were increased in the IMQ group. The knockdown of methylation-regulating enzyme ten-eleven translocation (TET) 2 expression in mice attenuated the expression levels of S100A9, SELL, IL7R, MMP9, CXCL1 and LCN2. Furthermore, the hydroxymethylated level of S100A9 was highly expressed in the IMQ group and was significantly decreased by TET2 deficiency in mice. On the whole, using an integrative system bioinformatics approach, the present study identified a series of characteristic enrichment pathways and key genes that may serve as potential biomarkers in psoriasis.