Identification and Validation of RNA Modification-Related Biomarkers in Dilated cardiomyopathy

Background The role of RNA modification-related genes (RMRGs) in Dilated cardiomyopathy (DCM) remains unclea. This study aimed to explore their contributions to HF pathogenesis. Methods Transcriptomic (GSE57338 and GSE42955) and single-cell RNA sequencing data (scRNA-seq) (GSE183852) were analyzed to identify RMRG-based biomarkers. Through integrating differential expression profiling, weighted gene co-expression network analysis (WGCNA), protein-protein interaction (PPI) networks, and machine learning algorithms, potential biomarkers were systematically identified. Predictive nomogram models targeting HF were established, complemented by subsequent functional enrichment studies, immune cell infiltration characterization, and therapeutic compound screening. Key cellular populations were determined through scRNA-seq technology, while reverse transcription quantitative PCR (RT-qPCR) served to clinically verify the expression patterns of candidate biomarkers. Results FURIN, STAT3, and BCL6 were identified as biomarkers. Enrichment analysis linked these biomarkers to pathways related to energy metabolism and immune regulation. Immune cell infiltration, specifically activated dendritic cells (aDCs), showed significant differences between HF and control groups ( p  < 0.05). Vincristine sulfate and ciglitazone were suggested as potential therapeutic agents for DCM. scRNA-seq identified endothelial cells and fibroblasts as key cells, with biomarkers showing distinct dynamic expression during their differentiation. RT-qPCR validation demonstrated markedly reduced expression of FURIN, STAT3, and BCL6 in HF patients relative to controls, aligning with computational predictions. Conclusions These three genes—FURIN, STAT3, and BCL6—emerged as RM-associated molecular signatures in HF pathophysiology, potentially informing novel therapeutic and preventive approaches.