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. 2021 Mar 22:2021:6626094.
doi: 10.1155/2021/6626094. eCollection 2021.

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

Yu Zeng  1 , Nanhong Li  2 , Zhenzhen Zheng  1 , Riken Chen  3 , Min Peng  1 , Wang Liu  1 , Jinru Zhu  1 , Mingqing Zeng  4 , Junfen Cheng  1 , Cheng Hong  3
Affiliations

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

Yu Zeng et al. Biomed Res Int. .

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.

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Conflict of interest statement

The authors have no conflicts of interest.

Figures

Figure 1
Figure 1
The workflow of this study.
Figure 2
Figure 2
Identification of DEGs from GSE117261 dataset. (a) Volcano plot of GSE117261 via R software. Log FC: log2 fold change. (b) Heat map of differentially expressed gene expression. The heat map was generated using pheatmap package in R. The expression profiles greater than the mean are colored in red, and those below the mean are colored in green. Blue, normal lung tissues; orange, PAH specimens. PAH: pulmonary arterial hypertension.
Figure 3
Figure 3
Top 10 enriched GO terms and top 10 KEGG pathways for differentially expressed genes. (a)–(c) GO term enrichment analysis for (a) biological process, (b) molecular function, and (c) cellular component. (d) KEGG pathway analysis. Node size represents gene ratio; node color represents P value. GO: Gene Ontology; KEGG: Kyoto Encyclopedia of Genes and Genomes.
Figure 4
Figure 4
Construction of the PPI network. The nodes represent proteins, and the edges represent the interaction of proteins, while blue and red circles indicate downregulated and upregulated DEGs, respectively.
Figure 5
Figure 5
Construction of the miRNA-TF-hub gene interaction network. The circles represent hub genes, the triangles represent miRNAs, and the diamond represent TFs, respectively.
Figure 6
Figure 6
The ROC curve was used to evaluate the diagnostic value of hub genes.
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References

    1. Ryan J. J., Archer S. L. The right ventricle in pulmonary arterial hypertension: disorders of metabolism, angiogenesis and adrenergic signaling in right ventricular failure. Circulation Research. 2014;115(1):176–188. doi: 10.1161/CIRCRESAHA.113.301129. - DOI - PMC - PubMed
    1. Runo J. R., Loyd J. E. Primary pulmonary hypertension. The Lancet. 2003;361(9368):1533–1544. doi: 10.1016/S0140-6736(03)13167-4. - DOI - PubMed
    1. Hoeper M. M., Humbert M., Souza R., et al. A global view of pulmonary hypertension. The Lancet Respiratory Medicine. 2016;4(4):306–322. doi: 10.1016/S2213-2600(15)00543-3. - DOI - PubMed
    1. Lau E. M. T., Giannoulatou E., Celermajer D. S., Humbert M. Epidemiology and treatment of pulmonary arterial hypertension. Nature Reviews Cardiology. 2017;14(10):603–614. doi: 10.1038/nrcardio.2017.84. - DOI - PubMed
    1. Benza R. L., Miller D. P., Barst R. J., Badesch D. B., Frost A. E., McGoon M. D. An evaluation of long-term survival from time of diagnosis in pulmonary arterial hypertension from the REVEAL registry. Chest. 2012;142(2):448–456. doi: 10.1378/chest.11-1460. - DOI - PubMed

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