What question did this study set out to answer?

This analysis investigates the genes and pathways contributing to gender differences in pulmonary arterial hypertension.

March 16, 2026Open Access

Identification of Key Genes and Pathways Associated With Gender Differences in Pulmonary Arterial Hypertension Based on Bioinformatic Approaches

Key Result

Among 741 female-specific DEGs in pulmonary arterial hypertension, 10 hub genes including SLC4A1 and THBS1 may play significant roles in the disease's pathogenesis in women.

Key Points

This analysis investigates the genes and pathways contributing to gender differences in pulmonary arterial hypertension.
Used microarray datasets GSE38267 and GSE131793 from GEO database.
Identified differentially expressed genes (DEGs) using volcano plots and Venn diagrams.
Performed Gene Ontology and KEGG pathway enrichment analyses for female-specific DEGs.
Analyzed protein-protein interactions of identified DEGs using the NetworkAnalyst tool.
Identified 741 unique female-specific DEGs and 10 potential hub genes.
GO analysis showed DEGs involved in cell-matrix adhesion and immune response.
Significant KEGG pathways include fluid shear stress and atherosclerosis.

Structured PICO

Population

Microarray datasets GSE38267 and GSE131793 from the GEO database containing samples from patients with pulmonary arterial hypertension (PAH) and healthy men and females.

Comparator

Healthy controls and male PAH patients

Outcome

Identification of female-specific differentially expressed genes (DEGs) and hub genes in PAHsurrogate

Bioinformatic analysis identified 10 female-specific hub genes that may help explain the gender differences in pulmonary arterial hypertension susceptibility and prognosis.

Main Result

Absolute Event Rate: 0% vs 0%

Abstract

Pulmonary arterial hypertension (PAH) is a complex disease with multiple contributing factors. Epidemiological data showed that women are more susceptible to PAH, but they tend to have better right ventricular (RV) function and prognosis compared to men. The mechanisms behind these gender differences are not well understood. Using a variety of bioinformatic techniques, this study was aimed at investigating the major genes and putative pathways driving PAH in females. Consequently, microarray datasets GSE38267 and GSE131793 were obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) in patients with PAH and healthy men and females were found via the use of volcano plots and Venn diagrams. Female‐specific DEGs were selected for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses, with results visualized via R and Cytoscape software. The protein–protein interactions (PPIs) of female‐specific DEGs were analyzed using the NetworkAnalyst online tool. Among identified DEGs, 98 DEGs were specific to males, 145 were shared among sexes, and 741 were unique to females. To focus on DEGs that are specific to female, male and shared DEGs were excluded. GO enrichment analysis revealed that these DEGs in females were mostly involved in cell–matrix adhesion, mucosal innate immune response, and hydrogen peroxide catabolism. Significant KEGG pathways included fluid shear stress, atherosclerosis, arrhythmogenic RV cardiomyopathy, and ECM–receptor interaction. Bioinformatic analysis of microarray datasets led to the identification of 10 female‐specific hub genes, SLC4A1 , THBS1 , ITGB3 , IL7R , CCR7 , SNCA , CTNNB1 , SELP , GZMK , and ITGA2B , from DEGs between control and PAH samples in females. These hub genes that are specific to females have the potential to be significant in the pathogenesis of PAH in females. These hub genes may be promising candidates for improving our knowledge of sex‐related processes in PAH; nevertheless, experimental confirmation is necessary before considering them as biomarkers or therapeutic targets.