Identification of potential core genes in idiopathic pulmonary arterial hypertension: An observational study highlighting the role of VEGFA

Idiopathic pulmonary arterial hypertension (IPAH) is a progressive disease characterized by unexplained pulmonary vascular resistance, which can lead to persistent pulmonary arterial hypertension and eventually right heart failure. A targeted therapy for IPAH that can effectively reduce pulmonary artery pressure and improve survival and prognosis is urgently required. This study aimed to identify potential core genes and pathways involved in the pathogenesis of IPAH through a bioinformatics approach. Two publicly available gene expression datasets (GSE15197 and GSE130391) from the Gene Expression Omnibus were analyzed in this observational study, encompassing 22 IPAH and 17 control lung specimens. The GEO2R tool was employed to identify differentially expressed genes. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway databases were employed for the functional enrichment analysis of the identified differentially expressed genes. STRING and Cytoscape were used to construct and visualize a protein-protein interaction network, respectively, for the identification of hub genes. A total of 159 genes were identified, of which 56 were downregulated and 103 were upregulated. Their biological functions mainly focus on negative regulation of transcription (DNA-templated), positive regulation of RNA polymerase II promoter transcription, zinc ion binding, and protein heterodimerization activity. Enrichment mapping revealed that the phosphatidylinositol 3-kinase-protein kinase B axis and cancer pathways constituted the central regulatory networks for the differentially expressed gene cohort. Ten hub genes were identified, including the notably downregulated core gene vascular endothelial growth factor A. While this STROBE-compliant study was computational in nature, the 10 hub genes identified present promising candidates for future exploration in IPAH prevention, diagnostic strategies, and therapeutic development. These findings should be interpreted as generating hypotheses that necessitate confirmation through rigorous experimental validation to establish their biological significance. Notably, vascular endothelial growth factor A emerged as a particularly intriguing and unanticipated differentially expressed gene, with its downregulation potentially representing a distinctive feature of IPAH among pulmonary hypertension subtypes.