Decoding mitochondrial stress genes in DCM: towards precision diagnosis and therapy.

Background: Mitochondrial oxidative stress (ROS) is a crucial factor in the pathogenesis of dilated cardiomyopathy (DCM). Despite its significance, robust biomarkers for assessing its role remain scarce. This study investigates ROS mechanisms in DCM and identifies associated biomarkers, offering fresh insights into diagnosis and treatment.

Methods: We sourced transcriptomic data from the GEO database and mitochondrial oxidative stress-related genes from GeneCards. Using consensus clustering, we identified 64 genes associated with mitochondrial oxidative stress in DCM and further isolated five hub genes through protein-protein interaction and machine learning techniques. These genes were analyzed for functions related to immunity, drug sensitivity, and single-cell localization. Concurrently, we collected blood samples from DCM patients to validate the hub genes' expression.

Results: The study identified five hub genes related to mitochondrial oxidative stress: VCL, ABCB1, JAK2, KDR, and NGF. Expression analysis revealed high levels of VCL, ABCB1, KDR, and NGF in the non-failing (NF) group, while JAK2 was elevated in the DCM group (p < 0.05). Diagnostic efficacy, measured by area under the curve (AUC), was significant for VCL (76.4), ABCB1 (80.1), JAK2 (68.2), KDR (78.1), and NGF (71.8). Moreover, several drugs were identified as potential regulators of these hub genes, including Topotecan, CDK9_5576, Acetalax, Afatinib, and GSK591. Notably, VCL showed increased expression in DCM patient blood samples, consistent with transcriptomic and single-cell findings.

Conclusion: This research highlights key genes associated with mitochondrial oxidative stress-VCL, ABCB1, JAK2, KDR, NGF-that show differential expression in DCM and myocardial infarction. These findings underscore their diagnostic potential and pave the way for new therapeutic strategies.