Decoding mitochondrial stress genes in DCM: towards precision diagnosis and therapy
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Bingbing Zhu1, Hai Cheng1, Jiawei Li1
1Department of Cardiology, Suzhou Kowloon Hospital, Shanghai Jiaotong University School of Medicine, Suzhou, Jiangsu Province, 215028, China.
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.
Insights
Researchers identified five key genes (VCL, ABCB1, JAK2, KDR, NGF) linked to mitochondrial oxidative stress in dilated cardiomyopathy (DCM). These genes show diagnostic potential and may lead to new therapeutic strategies for DCM.
Area of Science:
- Cardiology
- Genomics
- Biomarker Discovery
Background:
- Mitochondrial oxidative stress is a key factor in dilated cardiomyopathy (DCM) pathogenesis.
- Robust biomarkers for assessing oxidative stress in DCM are lacking.
- This study investigates oxidative stress mechanisms and biomarkers in DCM.
Purpose of the Study:
- To identify novel biomarkers for mitochondrial oxidative stress in DCM.
- To explore the diagnostic potential of identified biomarkers.
- To uncover potential therapeutic targets for DCM.
Main Methods:
- Transcriptomic data analysis from GEO database.
- Identification of hub genes using consensus clustering, protein-protein interaction, and machine learning.
- Validation of hub gene expression in DCM patient blood samples.
Main Results:
- Five hub genes (VCL, ABCB1, JAK2, KDR, NGF) associated with mitochondrial oxidative stress were identified.
- Differential expression of these genes was observed between non-failing and DCM groups.
- Significant diagnostic efficacy (AUC) was demonstrated for VCL, ABCB1, JAK2, KDR, and NGF.
Conclusions:
- VCL, ABCB1, JAK2, KDR, and NGF are key genes in mitochondrial oxidative stress relevant to DCM.
- These genes exhibit differential expression in DCM and myocardial infarction, indicating diagnostic potential.
- The findings pave the way for novel therapeutic strategies targeting oxidative stress in DCM.
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