Identification of plasma miR-4505, miR-4743-5p and miR-4750-3p as novel diagnostic biomarkers for coronary artery disease in patients with type 2 diabetes mellitus: a case-control study
Authors' conclusion
Our study revealed a unique profile of plasma-derived miRNAs in T2DM patients with CAD. Potential miRNA-regulated pathways were also identified, exploring the underlying pathogenesis of CAD in T2DM. We developed a specific three-miRNA panel of hsa-miR-4505, hsa-miR-4743-5p and hsa-miR-4750-3p, that could serve as a novel non-invasive biomarker for CAD in patients with T2DM.
Study context
- Population
- T2D patients with and without coronary artery disease (CAD), CAD patients and healthy controlsreplication cohort
- Participants
- 94 patients
- Comparison
- Plasma microRNAs (miRNAs) in T2D with CAD vs T2D without CAD, CAD and healthy controls
- Outcome
- Diagnostic value of plasma miRNAs for CAD in T2D (ROC analysis)
Methodological detailsmicroarray discovery stage, RT-qPCR replication cohort, Microarray profiling of 2,578 miRNAs; RT-qPCR validation; multivariate logistic regression diagnostic models
- Microarray discovery stage
- RT-qPCR replication cohort
- Microarray profiling of 2,578 miRNAs; RT-qPCR validation; multivariate logistic regression diagnostic models
Main finding
As reported in the abstract
Diagnostic performance for CAD in T2DM
| Group | AUC | Sensitivity | Specificity |
|---|---|---|---|
| Combination of three miRNAs | 0.959 | 100% | 86.67% |
Combination of three miRNAs
AUC0.959
Sensitivity100%
Specificity86.67%
- AUC of each validated miRNA for T2DM-CAD, good discriminatory value
- 0.833-0.876
- Dysregulation of miR-4505, miR-4743-5p and miR-4750-3p in T2DM-CAD vs T2DM and controls, confirmed by RT-qPCR
- all p < 0.001
Observational data: associations, not effects.
Further findings
Discovery-stage differentially expressed (DE)-miRNAs in T2DM-CAD
- Overexpressed: hsa-miR-4505, hsa-miR-4743-5p, hsa-miR-6846-5p
- Down-regulated: hsa-miR-3613-3p, hsa-miR-4668-5p, hsa-miR-4706, hsa-miR-6511b-5p, hsa-miR-6750-5p, hsa-miR-4750-3p, hsa-miR-320e, hsa-miR-4717-3p, hsa-miR-7850-5p
Pathway enrichment of DE-miRNA target genes
- Enriched in calcium ion binding, regulation of actin cytoskeleton and gene expression
- miR-4505, miR-4743-5p and miR-4750-3p involved in fatty acid metabolism, leukocyte transendothelial migration and neurotrophin signaling
Original publication
Identification of plasma miR-4505, miR-4743-5p and miR-4750-3p as novel diagnostic biomarkers for coronary artery disease in patients with type 2 diabetes mellitus: a case-control study. Cardiovasc Diabetol. Published 29 July 2024. doi:10.
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