Bioinformatics analysis of the GEO database for the identification of novel biomarkers and potential targeted drugs for pulmonary hypertension

Abstract

Pulmonary arterial hypertension (PAH) is a progressive and life-threatening cardiopulmonary disorder. This study integrated two PAH datasets (GSE117261 and GSE113439) from the Gene Expression Omnibus database to screen novel PAH biomarkers using bioinformatics methods and explore immune cell infiltration and potential therapeutic drugs. After batch effect correction, 311 differentially expressed genes (DEGs), comprising 182 upregulated and 129 downregulated genes, were identified using the Linear Models for Microarray Data analysis. Weighted gene co-expression network analysis revealed 11 significant modules, and intersecting these with DEGs yielded 24 module DEGs. Gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses indicated enrichment in extracellular matrix organization, exosome-related functions, and inflammation-related pathways, including the positive regulation of inflammatory response and acute-phase response. A protein-protein interaction network analysis identified 10 hub genes: Upregulated periostin, osteoblast-specific factor (POSTN), OGN, asporin, and downregulated S100 calcium-binding protein A12, LCN2, SPP1, S100 calcium-binding protein A9, CD163, S100A8, and AQP9. Immune infiltration analysis (CIBERSORT, dataset GSE169471) revealed markedly altered levels of monocytes, dendritic cells, neutrophils, resting cluster of differentiation 4-positive memory T cells, and macrophages. Single-cell RNA sequencing analysis further confirmed hub gene expression. Notably, macrophage-associated genes (SPP1, S100A8/A9/A12, CD163, POSTN, AQP9, and LCN2) were implicated in vascular inflammation, endothelial dysfunction, and fibrosis, underscoring their role in immune-mediated vascular remodeling in PAH. Finally, drug prediction using the Comparative Toxicogenomic Database identified retinol, arsenic trioxide, and active vitamin D as potential therapeutics with significant regulatory effects on hub genes. This integrated bioinformatics analysis reveals key genes, pathways, and immune cell alterations in PAH, emphasizing macrophage-associated mechanisms in vascular remodeling and immune dysregulation. The findings provide potential biomarkers and therapeutic targets for improved PAH management.

Keywords

Pulmonary arterial hypertension / Immune infiltration / Single-cell RNA sequencing / Weighted gene co-expression network analysis

Acknowledgments

None.

Funding

The study was funded by the Cultivation Project for Innovation Team in Teachers’ Teaching Proficiency by Zhengzhou Health College (No. 2024jxcxtd01).

Conflict of interest

Xin- Ying Ji is an Associate Editor and Umair Ali Khan Saddozai is an Editorial Board Member of this journal, but were not in any way involved in the editorial and peer-review process conducted for this paper, directly or indirectly. Separately, other authors declared that they have no known competing financial interests or personal relationships that could have influenced the work reported in this paper.

Author contributions

Conceptualization: Zhen-Dong Lu, Umair Ali Khan Saddozai

Data curation: Zhen-Dong Lu, Umair Ali Khan Saddozai

Formal analysis: Zhen-Dong Lu, Umair Ali Khan Saddozai

Funding acquisition: Xin-Ying Ji

Methodology: Zhen-Dong Lu, Xin-Ying Ji, Umair Ali Khan Saddozai

Project administration: Xin-Ying Ji, Umair Ali Khan Saddozai

Software: Zhen-Dong Lu, Umair Ali Khan Saddozai

Supervision: Xin-Ying Ji

Validation: Zhen-Dong Lu, Umair Ali Khan Saddozai

Writing - original draft: Zhen-Dong Lu, Umair Ali Khan Saddozai

Writing - review & editing: Zhi-Liang Jiang, Wahab Hussain, Xin-Ying Ji

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Availability of data

All data supporting the findings of this study are included within the article and its supplementary materials.

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