Exploration of Hub Genes in Retinopathy of Prematurity Based on Bioinformatics Analysis of the Oxygen-Induced Retinopathy Model

Abstract

Retinopathy of prematurity (ROP) is a major blindness-causing disease that is characterized by an arrest of normal vascular development and neovascularization of the retina. Previous studies have shown that genetic factors may be associated with the development and severity of ROP. However, the genes and mechanisms underlying ROP remain unclear. We aimed to identify hub genes in ROP and drugs related to these genes by integrative analysis. The expression profiles of GSE158799 and GSE135844 were acquired from the Gene Expression Omnibus (GEO) database, and differentially expressed genes (DEGs) were identified. Then, an integrative analysis was performed including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), gene set enrichment analysis (GSEA), protein-protein interaction (PPI) network, transcription factor (TF)-gene, and miRNA-gene networks analysis. Moreover, we verified hub genes and identified potential drugs. 225 common DEGs were identified. Biological function analysis indicated that angiogenesis, cell surface, cell adhesion, extracellular matrix, and focal adhesion genes were enriched among DEGs. The PI3K/Akt signalingpathway, focal adhesion, and extracellular matrix (ECM)-receptor interaction were markedly enriched in the KEGG pathway analysis. Finally, 5 hub genes related to the nosogenesis of ROP were identified and found to be targeted by VEGFA inhibitors, TLR4 antagonists, and sunitinib. The present study showed that VEGFA, ACTA2, MKI67, CD68, and TLR4 are potential hub genes involved in the pathogenesis of ROP. Moreover, TLR4 antagonists and sunitinib may be new candidate drugs for ROP therapy, in addition to VEGFA inhibitors.