Bioinformatics analysis of the GEO database for the identification of novel biomarkers and potential targeted drugs for pulmonary hypertension

Pulmonary arterial hypertension (PAH) is a progressive and life-threatening cardiopulmonary disorder. This study integrated two PAH datasets (GSE117261 and GSE113439) from the Gene Expression Omnibus database to screen novel PAH biomarkers using bioinformatics methods and explore immune cell infiltration and potential therapeutic drugs. After batch effect correction, 311 differentially expressed genes (DEGs), comprising 182 upregulated and 129 downregulated genes, were identified using the Linear Models for Microarray Data analysis. Weighted gene co-expression network analysis revealed 11 significant modules, and intersecting these with DEGs yielded 24 module DEGs. Gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses indicated enrichment in extracellular matrix organization, exosome-related functions, and inflammation-related pathways, including the positive regulation of inflammatory response and acute-phase response. A protein-protein interaction network analysis identified 10 hub genes: Upregulated periostin, osteoblast-specific factor (POSTN), OGN, asporin, and downregulated S100 calcium-binding protein A12, LCN2, SPP1, S100 calcium-binding protein A9, CD163, S100A8, and AQP9. Immune infiltration analysis (CIBERSORT, dataset GSE169471) revealed markedly altered levels of monocytes, dendritic cells, neutrophils, resting cluster of differentiation 4-positive memory T cells, and macrophages. Single-cell RNA sequencing analysis further confirmed hub gene expression. Notably, macrophage-associated genes (SPP1, S100A8/A9/A12, CD163, POSTN, AQP9, and LCN2) were implicated in vascular inflammation, endothelial dysfunction, and fibrosis, underscoring their role in immune-mediated vascular remodeling in PAH. Finally, drug prediction using the Comparative Toxicogenomic Database identified retinol, arsenic trioxide, and active vitamin D as potential therapeutics with significant regulatory effects on hub genes. This integrated bioinformatics analysis reveals key genes, pathways, and immune cell alterations in PAH, emphasizing macrophage-associated mechanisms in vascular remodeling and immune dysregulation. The findings provide potential biomarkers and therapeutic targets for improved PAH management.