Identification of autophagy-related biomarkers in patients with pulmonary arterial hypertension based on bioinformatics analysis.

Abstract

Autophagy participates in the regulation of pulmonary arterial hypertension (PAH). However, the role of autophagy-related genes (ARGs) in the pathogenesis of the PAH is still unclear. This study aimed to identify the ARGs in PAH via bioinformatics analysis. A microarray dataset (GSE113439) was downloaded from the Gene Expression Omnibus database to identify differentially expressed ARGs (DEARGs). Protein-protein interactions network, gene ontology, and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed to screen hub genes and the underlying molecular mechanisms of PAH. Finally, the mRNA expression of the hub genes was validated using the GSE53408 dataset. Twenty-six DEARGs were identified, all of which were upregulated. Enrichment analyses revealed that these DEARGs were mainly enriched in the nucleotide-binding oligomerization domain (NOD)-like receptor signaling pathway, PI3K-Akt signaling pathway, response to hypoxia, response to nutrient levels, and autophagy. Among these hub genes, the mRNA expression levels of HSP90AA1, HIF1A, MET, IGF1, LRRK2, CLTC, DNM1L, MDM2, RICTOR, and ROCK2 were significantly upregulated in PAH patients than in healthy individuals. Ten hub DEARGs were identified and may participate in the pathogenesis of the PAH via the regulation of autophagy. The present study may provide novel therapeutic targets for PAH prevention and treatment and expand our understanding of PAH.