Identification of endoplasmic reticulum stress-associated signatures of human pulmonary arterial hypertension: A bioinformatic analysis

Pulmonary arterial hypertension (PAH) is a group of complex vasculopathies characterized by increased pulmonary arterial pressure and subsequent pulmonary vascular remodeling. However, the underlying pathogenesis of PAH has not been fully elucidated. In the present study, we employed bioinformatics technology to investigate the pathogenesis of PAH. Microarray datasets related to PAH were retrieved from the Gene Expression Omnibus database to screen for ER stress-related genes (ERSRGs) between normal control and PAH samples. The differentially expressed genes (DEGs) were analyzed for functional enrichment and protein‒protein interaction (PPI) networks. DEG-related miRNAs and transcriptional factor (TF) were predicted to construct the miRNA-TF-hub gene network. The diagnostic accuracy of the hub genes was assessed via receiver operating characteristic (ROC) curve analysis. The relative abundances of different types of immune cells were determined via immune infiltration analysis. The screening detected 20 ERSRGs between normal and PAH samples, nine of which (HIF1A, BCL2L1, TLR4, HMOX1, VCAM1, EGR1, MAPK8, LCN2, and CEBPB) were further identified as hub genes via the PPI network. To construct a regulatory network analysis of the Hub genes, 57 miRNAs and 35 TFs were subsequently predicted. There was a significant difference in the infiltration of 17 types of immune cells between the two groups. These results suggest that the nine hub genes might play crucial roles in the development of PAH. These findings might provide new therapeutic targets for PAH or potential biomarkers for its diagnosis.