Identification of ion homeostasis-related genes as diagnostic biomarkers for pulmonary arterial hypertension via WGCNA and machine learning.

S1PR1, CA2, and ABCG2 are identified as potential diagnostic biomarkers for pulmonary arterial hypertension, with S1PR1 showing a protective role in endothelial cells.

• Why it matters: Early diagnosis of PAH remains challenging, and understanding the regulatory network of ion homeostasis-related genes (IHRGs) could improve diagnostic strategies and reveal mechanisms underlying disease progression.
• What they did: Using WGCNA on GSE117261 and three machine learning algorithms, researchers screened 55 IHRGs and validated nine core genes, including S1PR1, CA2, and ABCG2, in two datasets, complemented by bioinformatics and in vitro hypoxia experiments.
• The result: The study suggests that IHRGs influence PAH development through ion homeostasis and endothelial function modulation, with S1PR1 providing endothelial protection and CA2 involved in hypoxia adaptation, offering new avenues for early diagnosis and mechanistic research.