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Journal Article
Review
Roles of the crucial mitochondrial DNA in hypertrophic cardiomyopathy prognosis and diagnosis: A review.
Medicine (Baltimore) 2023 December 2
Mitochondrial DNA is implicated in hypertrophic cardiomyopathy (HCM) development. We aimed to identify valuable mtDNAs that contribute to the development of HCM. Differentially expressed mitochondrial DNAs (DEMGs) between HCM and controls were screened. GO and KEGG functional enrichment analyses were performed, and the optimum genes were explored using the LASSO regression mode and SVM-RFE model. A diagnostic scoring model was constructed and verified using ROC curves. Mitochondria-based subtypes were identified. Immune performance among the subtypes including immune cells, immune checkpoint genes, and HLA family genes was analyzed. Finally, an mRNA-transcription factor (TF)-miRNA network was constructed using Cytoscape software. Twelve DEMGs in HCM were selected. Among them, 6 DEMGs, including PDK4, MGST1, TOMM40, LYPLAL1, GATM, and CPT1B were demonstrated as DEMGs at the point of intersection of Lasso regression and SVM-RFE. The ROC of the model for the training and validation datasets was 0.999 and 0.958, respectively. Two clusters were divided, and 4 immune cell types were significantly different between the 2 clusters, including resting mast cells, macrophages M2, and plasma cells. Nine upregulated KEGG pathways were enriched in cluster 1 vs. cluster 2 including O-glycan biosynthesis, the ErbB signaling pathway, and the GnRH signaling pathway. Meanwhile, 49 down-regulated pathways were enriched such as the toll-like signaling pathway and natural killer cell-mediated cytotoxicity pathway. The 6 gene-based mRNA-TF-miRNA networks included other 133 TFs and 18 miRNAs. Six DEMGs in HCM, including PDK4, MGST1, TOMM40, LYPLAL1, GATM, and CPT1B, can be indicative of HCM prognosis or disease progression.
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