Identification of Differentially Expressed ER Stress-Related Genes and Their Association with Pulmonary Arterial Hypertension

Abstract

Abstract Pulmonary arterial hypertension (PAH) is a progressive disease with a complex etiology, a high mortality rate, and strong harm. Endoplasmic reticulum (ER) stress and immune infiltration are key to the pathogenesis of PAH, but their interaction in PAH is still unclear. In this study, we investigated the role of ER stress and immune infiltration in PAH and their interrelationships using bioinformatics methods. Gene expression profiles and ER stress-related genes were downloaded from the Gene Expression Omnibus (GEO) and MSigDB databases, respectively. A total of 31 differentially expressed ER stress-related genes highly associated with PAH were identified by the Limma software package and weighted gene co-expression network analysis (WGCNA). Enrichment analysis showed that these genes were mainly enriched in response to endoplasmic reticulum stress, response to unfolded proteins, protein transport, and protein processing in the endoplasmic reticulum. Subsequently, the identification of the top five hub genes (EIF2S1, NPLOC4, SEC61B, SYVN1, and DERL1) was accomplished through screening within the protein-protein interaction (PPI) network. Immune infiltration analysis showed that these hub genes were closely related to immune cells. The receiver operating characteristic (ROC) curves showed that hub genes had a good diagnostic value for PAH. Ultimately, a rat model of pulmonary arterial hypertension (PAH) was successfully established, wherein the observed expression levels of SEC61B, NPLOC4, and EIF2S1 in the PAH group aligned with the outcomes derived from bioinformatics analysis. The SEC61B, NPLOC4, and EIF2S1 identified in this study could be used as potential biomarkers. This study provided new potential therapeutic targets for the prevention and treatment of PAH.