Identification of RUNX1 as a Biomarker for Right Ventricular Remodeling in Pulmonary Arterial Hypertension Using WGCNA

ABSTRACT Right ventricle (RV) dysfunction is central to pulmonary arterial hypertension (PAH) yet its molecular mechanisms remain unclear. This study aimed to identify biomarkers and therapeutic targets for RV remodeling in PAH. The dataset GSE240941 have 39 RV tissue samples, including normal RV, compensated RV (comRV), and decompensated RV (decomRV). Differential analysis revealed no significant gene differences between comRV and normal RV tissues but identified 2384 different expression genes between decomRV and normal RV tissues. Weighted gene co‐expression network analysis (WGCNA) highlighted the Coral2 module as strongly associated with decomRV remodeling (cor = 0.51, p = 0.01). Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses of Coral2 module identified potential mechanisms and 78 hub genes (|MM | > 0.80 and |GS | > 0.50). Among these hub genes, CDK2, ITGB3, and RUNX1 emerged as key candidates through further filtering and CytoHubba analysis. While all three genes showed elevated expression in the training set, only RUNX1 was significantly upregulated in the validation dataset (GSE120852). RT‐qPCR and western blot from RV tissue of monocrotaline‐induced pulmonary hypertension rats showed that RUNX1 was significantly elevated in RV tissue. Immunofluorescence indicated that RUNX1 was primarily localized in the nucleus. Receiver operating characteristic curve analysis demonstrated the ability of CDK2, ITGB3, and RUNX1 to differentiate decomRV remodeling in training dataset and validating dataset. Based on the results of WGCNA and preliminary validation from animal experiments, RUNX1 may be a potential biomarker for RV failure in the context of PAH.