Bioinformatics analyses reveal the autophagy-related feature biomarkers in dilated cardiomyopathy with heart failure

Objective Dilated cardiomyopathy (DCM) is a major cause of heart failure (HF). In this study, we aimed to explore potential autophagy-related biomarkers associated with DCM with HF. Methods The GSE17800 dataset was downloaded from GEO, and differentially expressed genes (DEGs) were identified. Autophagy-related DEGs (AR-DEGs) were obtained by merging DEGs with autophagy-related genes (ARGs) from HADb and HAMdb databases. Gene function enrichment analysis was performed using GO and KEGG. Hub genes were identified via protein-protein interaction (PPI) network analysis, with their expression and diagnostic values validated using the GSE21610 dataset. A doxorubicin (DOX)-induced cardiomyocyte injury model was established to evaluate hub gene expression in vitro and in vivo studies. Potential therapeutic small molecules targeting hub genes were screened via L1000FWD, and their binding affinity to targets was assessed by molecular docking. Results In the GSE17800 dataset, a total of 45 AR-DEGs were identified by intersecting with ARGs from HADb and HAMdb. Through PPI network analysis, 7 hub genes were extracted: CDKN1A, CTSD, DDIT3, EP300, FN1, PKM, and SOD2. Further validation using the GSE21610 dataset showed that receiver operating characteristic (ROC) curve analysis confirmed CTSD and SOD2 had high diagnostic value for DCM with HF. Moreover, in both in vitro and in vivo DOX-induced cardiomyocyte injury models, DOX treatment resulted in upregulated CTSD expression and downregulated SOD2 expression. Additionally, small molecules targeting CTSD and SOD2 (e.g., QL-XII-47 and tipifarnib-P2) were identified as potential therapeutic candidates for DCM with HF. Conclusion This study provides novel evidence that CTSD and SOD2 potently contribute to autophagy regulation in DCM with HF. These findings highlight their diagnostic potential for DCM with HF and lay a foundation for exploring targeted small-molecule therapies (e.g., QL-XII-47, tipifarnib-P2) to improve the disease's clinical management.