Integrated bioinformatics analysis reveals novel key biomarkers and potential candidate small molecule drugs in diabetic nephropathy

Abstract

The underlying molecular mechanisms of diabetic nephropathy (DN) have yet not been investigated clearly. In this investigation, we aimed to identify key genes involved in the pathogenesis and prognosis of DN. We selected expression profiling by high throughput sequencing dataset GSE142025 from Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) between DN and normal control samples were analyzed with limma package. Gene ontology (GO) and REACTOME enrichment analysis were performed using ToppGene. Then we established the protein-protein interaction (PPI) network, miRNA-DEG regulatory network and TF-DEG regulatory network. The diagnostic values of hub genes were performed through receiver operating characteristic (ROC) curve analysis. Finally, the candidate small molecules as potential drugs to treat DM were predicted using molecular docking studies. Through expression profiling by high throughput sequencing dataset, a total of 549 DEGs were detected including 275 up regulated and 274 down regulated genes. Biological process analysis of functional enrichment showed these DEGs were mainly enriched in cell activation, response to hormone, cell surface, integral component of plasma membrane, signaling receptor binding, lipid binding, immunoregulatory interactions between a lymphoid and a non-lymphoid cell and biological oxidations. DEGs with high degree of connectivity (MDFI, LCK, BTK, IRF4, PRKCB, EGR1, JUN, FOS, ALB and NR4A1) were selected as hub genes from protein-protein interaction (PPI) network, miRNA-DEG regulatory network and TF-DEG regulatory network. The ROC curve analysis confirmed that hub genes were high diagnostic values. Finally, the significant small molecules were obtained based on molecular docking studies. Our results indicated that MDFI, LCK, BTK, IRF4, PRKCB, EGR1, JUN, FOS, ALB and NR4A1 could be the potential novel biomarkers for GC diagnosis prognosis and the promising therapeutic targets. The present study may be crucial to understanding the molecular mechanism of DN initiation and progression.