Mining the proliferative diabetic retinopathy-associated genes and pathways by integrated bioinformatic analysis

Diabetic retinopathy (DR) especially proliferative diabetic retinopathy (PDR) is a serious eye disease. We aimed to identify key pathway and hub genes associated with PDR by analyzing the expression of retinal fibrovascular tissue in PDR patients.

First raw data were downloaded from the Gene Expression Omnibus database. Median normalization was subsequently applied to preprocess. Differentially expressed genes (DEGs) analyzed with the Limma package. Weighted correlation network analysis (WGCNA) was utilized to build the co-expression network for all genes. Then, we compared the DEGs and modules filtered out by WGCNA. A protein-protein interaction network based on the STRING web site and the Cytoscape software was constructed by the overlapping DEGs. Next, the Gene Ontology term and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed. Finally, we used the Comparative Toxicogenomics Database to identify some important pathways and hub genes tightly related to PDR.

Functional enrichment analysis showed that the pathway of cytokine-cytokine receptor interaction was significantly related to PDR eight hub genes which were associated with pathway including tumor necrosis factor (TNF), tumor necrosis factor receptor superfamily member 12A (TNFRSF12A), C-C chemokine 20 (CCL20), chemokine (C-X-C motif) ligand 2 (CXCL2), oncostatin M (OSM) interleukin 10 (IL10), interleukin 15 (IL 15), and interleukin 1B (IL1B).

We identified one pathway and eight hub genes, which were associated with PDR. The pathway provided references that will advance the understanding of mechanisms of PDR. Moreover, the hub genes may serve as therapeutic targets for precise diagnosis and treatment of PDR in the future.