Identification of common genes associated with diabetic nephropathy and diabetic retinopathy

There is a common basis of the diabetic nephropathy (DN) and diabetic retinopathy (DR), but the common genes of DN and DR were unclear.

In this study, DN-related and DR-related transcriptome data GSE185011 was extracted. Firstly, the differentially expressed genes 1 (DEGs1) between DN and normal control (HC) samples, and DEGs2 between DR and HC samples were screened by "limma". Then, the common genes of DN and DR were obtained by intersecting the DEGs1 and DEGs2. Next, the enrichment analyses of DEGs1 and DEGs2 were conducted by "ClusterProfiler", and the enrichment analysis of common genes was conducted by "Metascape". Moreover, the diagnostic genes were screened out by least absolute shrinkage and selection operator (LASSO) analysis, and the gene set enrichment analysis (GSEA) of diagnostic genes was performed. Furthermore, the immune cell infiltration analysis was used to further study the differences of disease mechanisms. In addition, the TF-mRNA-miRNA regulatory networks were constructed to reveal the potential regulation of diagnostic genes at the molecular level.

A totals of 206 common genes were obtained by intersecting the 526 DEGs1 and 1,059 DEGs2. Then, 6 diagnostic genes (METTL27, NMNAT2, TTC25, GAS6, ATP4A and ZNF223) of DN and 4 diagnostic genes (MCOLN3, C17orf77, ENPP3 and ATP4A) of DR were screened out. Notably, the proportion of central memeory CD4 T cells was significantly decreased in DN groups, and activated B cells was significantly increased in DR groups. Furthermore, the 493 TF-6mRNA-183miRNA regulatory network of DN and 111 TF-4mRNA-33miRNA regulatory network of DR were constructed, among them, hsa-mir-101-3p was the common miRNA for ZNF223, NMNAT2 and TTC25, and EGR1 was the key TF which could regulate ATP4A, GAS6, METTL27, NMNAT2 and TTC25 at the same time.

This study revealed the potential molecular mechanisms of diagnostic genes in DN and DR, which could provide novel insights for the clinical diagnosis and treatment of DN and DR.