Bioinformatics for the Identification of STING-Related Genes in Diabetic Retinopathy

Diabetic retinopathy (DR) is the most common complication of diabetes mellitus. Stimulator of interferon genes (STING) plays an important regulatory role in the transcription of several genes. This study aimed to mine and identify hub genes relevant to STING in DR.

The STING-related genes (STING-RGs) were extracted from MSigDB database. Differentially expressed STING-RGs (DE-STING-RGs) were filtered by overlapping differentially expressed genes (DEGs) between DR and NC specimens and STING-RGs. A PPI network was established to mine hub genes. The ability of the hub genes to differentiate between DR and NC specimens was evaluated. Additionally, a ceRNA network was established to investigate the regulatory mechanisms of hub genes. Subsequently, the discrepancies in immune infiltration between DR and NC specimens were further explored. Additionally, we performed drug predictions. Finally, RT-qPCR of peripheral blood samples was used to validate the bioinformatics results.

A grand total of four genes (IKBKG, STAT6, NFKBIA, and FCGR2A) related to STING were identified for DR. The AUC values of all four hub genes were greater than 0.7, which indicated that the diagnostic value was acceptable. The ceRNA network contained four hub genes, 170 miRNAs, and 135 lncRNAs. In addition, immunoinfiltration analysis demonstrated that the abundance of activated B cells was notably different between the DR and NC specimens. Moreover, 32 drugs were included in the drug-gene network, with twelve drugs targeting STAT6, nine drugs targeting NFKBIA, four drugs targeted IKBKG, and seven drugs targeted FCGR2A. The expression of the four hub genes in blood samples determined by RT-qPCR was consistent with our analysis.

In conclusion, four hub genes (IKBKG, STAT6, NFKBIA, and FCGR2A) related to STING with a diagnostic value for DR were identified by bioinformatics analysis, which might provide new insights into the evaluation and treatment of DR.