Identifying DUSP-1 and FOSB as hub genes in immunoglobulin A nephropathy by WGCNA and DEG screening and validation

Abstract

Background The mechanism of immunoglobulin A nephropathy (IgAN) is still unknown. A bioinformatics analysis is a powerful method to identify the biomarkers and possible therapeutic targets of a certain disease from related datasets. Methods The GSE93973 dataset, obtained from the Gene Expression Omnibus (GEO) database, was used to construct a weighted gene co-expression network (WGCNA) and filter differentially expressed genes (DEGs). The biological process (BP) enrichment among all the genes in the key modules was analyzed through a Gene Ontology (GO) enrichment analysis. We selected the overlap of hub genes in the WGCNA and Protein-Protein Interaction (PPI) network as the final hub genes in IgAN. We verified the final hub genes in two other datasets and in clinical kidney tissue specimens. A receiver operating characteristic (ROC) curve was used to evaluate the diagnostic efficacy of hub genes for IgAN. Results The turquoise module, which contained 1,806 genes, was the module with the highest correlation coefficient with IgAN in the GSE93973 dataset. The GO enrichment analysis showed that these 1,806 genes were mainly enriched in inflammation and immune responses. There were five hub genes identified by WGCNA and 34 hub genes identified in a DEG analysis in the GSE93973 dataset. DUSP1 and FOSB were identified as the final hub genes in IgAN. The validation results of the final hub genes in two other databases and clinical kidney tissue specimens validated the result that, compared to the control group, FOSB and DUSP1 were expressed at lower levels in the glomerulus of IgAN patients. The ROC curve indicated that DUSP1 and FOSB were good diagnostic indicators for IgAN. Conclusions Our analysis identified two hub genes that might be potential targets for the intervention and treatment of IgAN.