Gene expression and immune cell infiltration are essential in the etiopathogenesis of pulmonary arterial hypertension (PAH). Our study attempted to identify novel differentially co-expressed genes and to investigate the features of immune cell infiltration in PAH.

Material and methods:
The GSE113439 and GSE117261 datasets were acquired from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) between the PAH and control groups were identified based on the GSE117261 dataset. Weighted gene co-expression network analysis (WGCNA) was used to analyze the pre-processed data. Functional enrichment analysis was then carried out to explore the biological functions of these gene modules. The differentially co-expressed key gene modules were verified in-depth by GEO2R analysis. The immune infiltration in PAH was investigated by cell type identification by estimating relative subsets of RNA transcripts (CIBERSORT).

The WGCNA analysis found 15 differentially co-expressed gene modules, with the blue module indicating the strongest positive link to PAH and the green module indicating the strongest nega­tive association with PAH. The kyoto encyclopedia of genes and genomes (KEGG) pathway analysis showed that the genes in the blue module were largely enriched in lysosome, complement, and coagulation cascades, and others, whereas the genes in the green module were primarily enriched in the chemokine signaling pathway, platelet activation, etc. Integrin subunit alpha M (ITGAM) was identified as the differentially co-expressed key gene. Immune infiltration analysis by CIBERSORT showed the differences between the PAH and control groups or between the PAH subgroups.

ITGAM was considered a promising biomarker to discriminate PAH from the controls. Obvious differences were observed in immune infiltration between patients with the PAH and normal groups, providing new insight into understanding the molecular mechanisms on PAH’s pathogenesis.