Key result
Bioinformatics analysis and clinical validation identified 13 differentially expressed miRNAs with an AUC value greater than 0.9 for diagnosing dilated cardiomyopathy.
Why the study?
Dilated cardiomyopathy is prevalent, but the molecular mechanisms underlying its pathogenesis and progression remain poorly understood.
Observational (n=170)
Effect estimate: AUC > 0.9
Identified a miRNA-mRNA regulatory network and 13 specific miRNAs with high diagnostic potential (AUC > 0.9) for dilated cardiomyopathy.
Warrants no practice change in DCM; leaves open validation of identified targets in prospective studies.
Background: Although dilated cardiomyopathy (DCM) is a prevalent form of cardiomyopathy, the molecular mechanisms underlying its pathogenesis and progression remain poorly understood. It is possible to identify and validate DCM-associated genes, pathways, and miRNAs using bioinformatics analysis coupled with clinical validation methods. Methods: Our analysis was performed using 3 mRNA datasets and 1 miRNA database. We employed several approaches, including gene ontology (GO) analysis, KEGG pathway enrichment analysis, protein-protein interaction networks analysis, and analysis of hub genes to identify critical genes and pathways linked to DCM. We constructed a regulatory network for DCM that involves interactions between miRNAs and mRNAs. We also validated the differently expressed miRNAs in clinical samples (87 DCM ,83 Normal) using qRT-PCR.The miRNAs' clinical value was evaluated by receiver operating characteristic curves (ROCs). Results: 78 differentially expressed genes (DEGs) and 170 differentially expressed miRNAs (DEMs) were associated with DCM. The top five GO annotations were collagen-containing extracellular matrix, cell substrate adhesion, negative regulation of cell differentiation, and inflammatory response. The most enriched KEGG pathways were the Neurotrophin signaling pathway, Thyroid hormone signaling pathway, Wnt signaling pathway, and Axon guidance. In the PPI network, we identified 10 hub genes, and in the miRNA-mRNA regulatory network, we identified 8 hub genes and 15 miRNAs. In the clinical validation, we found 13 miRNAs with an AUC value greater than 0.9. Conclusion: Our research offers novel insights into the underlying mechanisms of DCM and has implications for identifying potential targets for diagnosis and treatment of this condition.
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Chen et al. (2024) conducted an observational in Dilated cardiomyopathy (n=170). Differentially expressed miRNAs vs. Normal controls was evaluated on Diagnostic value of miRNAs (AUC) (AUC > 0.9). Bioinformatics analysis and clinical validation identified 13 differentially expressed miRNAs with an AUC value greater than 0.9 for diagnosing dilated cardiomyopathy.
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