Disulfidptosis-Related Genes as Novel Biomarkers and Therapeutic Targets in Dilated Cardiomyopathy

Dilated cardiomyopathy (DCM) is a severe cardiac condition characterized by ventricular dilation and impaired systolic function, leading to heart failure and sudden death. Current treatments have limited efficacy in reversing disease progression. Recent research suggests that disulfidptosis, a novel cell death mechanism, may play a role in DCM pathogenesis, though its specific involvement remains unclear.

This study utilized multiple GEO datasets to analyze the expression of 24 disulfidptosis-related genes (DiGs) in DCM patients and healthy controls. Differential expression analysis and consensus clustering were used to classify DCM patients into subgroups based on DiGs expression profiles. A predictive model was constructed using four machine learning methods, and its performance was validated with independent datasets. A ceRNA regulatory network was established, and in vivo experiments were conducted using a DCM mouse model to validate key findings.

Nineteen DiGs were differentially expressed between DCM and controls. Consensus clustering divided DCM patients into two subtypes with distinct immune profiles. The support vector machine (SVM) model demonstrated superior diagnostic performance (AUC = 0.983), identifying ACTN4, MYH10, TLN1, DSTN, and NCKAP1 as core predictors. In vivo validation confirmed their expression changes in myocardial tissue. Single-cell RNA-seq further revealed increased fibroblast and macrophage infiltration in DCM, along with enrichment of fibrotic and immune pathways. Quercetin and resveratrol were predicted as potential drugs targeting these core genes.

This study demonstrates that ACTN4, MYH10, TLN1, DSTN, and NCKAP1 play significant roles in the pathogenesis of DCM, influencing immune cell infiltration and metabolic homeostasis. Quercetin and resveratrol were identified as potential therapeutic agents, offering new directions for DCM treatment.