Abstract
Abstract
Background
Pulmonary arterial hypertension (PAH) is characterized by a progressive increase in pulmonary vascular resistance and pulmonary arterial pressure, with complex etiology, difficult treatment and poor prognosis. The objective of this study was to investigate the potential biomarkers for PAH based on bioinformatics analysis.
Methods
The GSE117261 datasets were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified by screening PAH patients and controls. Then the DEGs were analyzed using a Weighted Gene Co-expression Network Analysis (WGCNA) and the key modules were determined, and to further explore their potential biological functions via Gene Ontology analysis (GO), Kyoto Encyclopedia of Genes and Genomes Pathway analysis (KEGG), and Gene Set Enrichment Analysis (GSEA). Moreover, Protein–protein interaction (PPI) networks were constructed to identify hub gene candidates in the key modules. Finally, real-time quantitative polymerase chain reaction was supplied to detect the expressions of hub genes in human pulmonary arterial smooth cells treated with cobalt chloride (COCl2) which was used to mimic hypoxia.
Results
There were 2299 DEGs identified. WGCNA indicated that yellow module was the key one correlated with PAH. GO and KEGG analysis demonstrated that genes in the yellow module were mainly enriched in ‘Pathways in cancer’. GSEA revealed that ‘HALLMARK_MYC_TARGETS_V1’ was remarkably enriched in PAH. Based on the PPI network, vascular endothelial growth factor A, proto-oncogene receptor tyrosine kinase (KIT), PNN interacting serine and arginine rich protein (PNISR) and heterogeneous nuclear ribonucleoprotein H1 (HNRNPH1) were identified as the hub genes. Additionally, the PCR indicated that the elevated expressions of PNISR and HNRNPH1 were in line with the bioinformatics analysis. ROC analysis determined that PNISR and HNRNPH1 may be potential biomarkers to provide better diagnosis of PAH.
Conclusion
PNISR and HNRNPH1 were potential biomarkers to diagnosis PAH. In summary, the identified DEGs, modules, pathways, and hub genes provide clues and shed light on the potential molecular mechanisms of PAH.
Funder
National Natural Science Foundation of China
Joint Funds for the Innovation of Science and Technology, Fujian province
Publisher
Springer Science and Business Media LLC
Subject
Pulmonary and Respiratory Medicine
Reference45 articles.
1. Klinger JR. novel pharmacological targets for pulmonary arterial hypertension. Compr Physiol. 2021;11(4):2297–349.
2. Barnett CF, Alvarez P, Park MH. Pulmonary arterial hypertension: diagnosis and treatment. Cardiol Clin. 2016;34(3):375–89.
3. Zhang JR, Ouyang X, Hou C, Yang QF, Wu Y, Lu WJ, Liu CL, Yang K, Zhong NS, Wang J, et al. Natural ingredients from Chinese materia medica for pulmonary hypertension. Chin J Nat Med. 2021;19(11):801–14.
4. Bisserier M, Pradhan N, Hadri L. Current and emerging therapeutic approaches to pulmonary hypertension. Rev Cardiovasc Med. 2020;21(2):163–79.
5. Zhao E, Xie H, Zhang Y. Identification of differentially expressed genes associated with idiopathic pulmonary arterial hypertension by integrated bioinformatics approaches. J Comput Biol. 2021;28(1):79–88.