Screening of Hub Genes Associated with Pulmonary Arterial Hypertension by Integrated Bioinformatic Analysis

Yu Zeng; Nanhong Li; Zhenzhen Zheng; Riken Chen; Min Peng; Wang Liu; Jinru Zhu; Mingqing Zeng; Junfen Cheng; Cheng Hong

doi:10.1155/2021/6626094

Screening of Hub Genes Associated with Pulmonary Arterial Hypertension by Integrated Bioinformatic Analysis

Biomed Res Int. 2021 Mar 22:2021:6626094. doi: 10.1155/2021/6626094. eCollection 2021.

Authors

Yu Zeng¹, Nanhong Li², Zhenzhen Zheng¹, Riken Chen³, Min Peng¹, Wang Liu¹, Jinru Zhu¹, Mingqing Zeng⁴, Junfen Cheng¹, Cheng Hong³

Affiliations

¹ Department of Respiration, The Second Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China.
² Institute of Nephrology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China.
³ China State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.
⁴ First Clinical School of Medicine, Guangdong Medical University, Zhanjiang, Guangdong, China.

Abstract

Background: Pulmonary arterial hypertension (PAH) is a disease or pathophysiological syndrome which has a low survival rate with abnormally elevated pulmonary artery pressure caused by known or unknown reasons. In addition, the pathogenesis of PAH is not fully understood. Therefore, it has become an urgent matter to search for clinical molecular markers of PAH, study the pathogenesis of PAH, and contribute to the development of new science-based PAH diagnosis and targeted treatment methods.

Methods: In this study, the Gene Expression Omnibus (GEO) database was used to downloaded a microarray dataset about PAH, and the differentially expressed genes (DEGs) between PAH and normal control were screened out. Moreover, we performed the functional enrichment analyses and protein-protein interaction (PPI) network analyses of the DEGs. In addition, the prediction of miRNA and transcriptional factor (TF) of hub genes and construction miRNA-TF-hub gene network were performed. Besides, the ROC curve was used to evaluate the diagnostic value of hub genes. Finally, the potential drug targets for the 5 identified hub genes were screened out.

Results: 69 DEGs were identified between PAH samples and normal samples. GO and KEGG pathway analyses revealed that these DEGs were mostly enriched in the inflammatory response and cytokine-cytokine receptor interaction, respectively. The miRNA-hub genes network was conducted subsequently with 131 miRNAs, 7 TFs, and 5 hub genes (CCL5, CXCL12, VCAM1, CXCR1, and SPP1) which screened out via constructing the PPI network. 17 drugs interacted with 5 hub genes were identified.

Conclusions: Through bioinformatic analysis of microarray data sets, 5 hub genes (CCL5, CXCL12, VCAM1, CXCR1, and SPP1) were identified from DEGs between control samples and PAH samples. Studies showed that the five hub genes might play an important role in the development of PAH. These 5 hub genes might be potential biomarkers for diagnosis or targets for the treatment of PAH. In addition, our work also indicated that paying more attention on studies based on these 5 hub genes might help to understand the molecular mechanism of the development of PAH.

MeSH terms

Computational Biology*
Databases, Nucleic Acid*
Gene Expression Profiling*
Gene Regulatory Networks*
Humans
Microarray Analysis*
Protein Interaction Maps*
Pulmonary Arterial Hypertension* / genetics
Pulmonary Arterial Hypertension* / metabolism