Integrated Bioinformatics Analysis Reveals Marker Genes and Immune Infiltration for Pulmonary Arterial Hypertension

Background: It is well known that Pulmonary arterial hypertension (PAH) is a chronic cardiopulmonary syndrome with high pulmonary vascular load and eventually causing RV heart failure even death. This research is aimed to detect the underlying key genes and potential mechanism of PAH using some kinds of bioinformatic tools. Methods The gene microarrays GSE22356, GSE131793 and GSE168905 were acquired from the GEO. Subsequently, a host of bioinformatics techniques, for instance, DAVID for GO annotation and KEGG enrichment analysis, STING for PPI, Cytoscape software etc. were utilized to investigate DEGs between PAH and healthy controls. Additionally, we also predicted the transcription factors regulating DEGs. And CIBERSORT was used to conduct immune infiltration analysis. Results we identified 403 up-regulated DEGs and 874 down-regulated DEGs in peripheral blood samples between 32 PAH patients and 29 controls. These functional changes of DEGs were mainly enriched in protein binding, extracellular exosome, extracellular space, extracellular region and integral component of plasma membrane. SLC4A1, AHSP, ALAS2, CA1, HBD, SNCA, HBM, SELENBP1, SERPINE1 and ITGA2B were detected as hub genes. These key genes are chiefly enriched at extracellular exosome, hemoglobin complex, blood microparticle, oxygen transporter activity. Among TF-DEGs network, 42 target DEGs and 6 TFs were predicted with an NES > 4 (TEAD4, TGIF2LY, GATA5, GATA1, GATA2, FOS). Immune infiltration analysis showed that monocytes occupied the largest proportion of immune cells. Conclusion We detected SLC4A1, AHSP, ALAS2, CA1, HBD, SNCA, HBM, SELENBP1, SERPINE1 and ITGA2B as the most significant markers of PAH. The PAH patients had higher infiltration of NK cell activation, monocyte, T cell CD4 memory activation, and mast cell than healthy controls and lower infiltration of T cell CD4 naive. These identified genes and these immune cells probably have precise regulatory relationships in the development of PAH.