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Published on: July 3, 2018
Circulating miRNA-Protein Signatures Predict Outcomes in Pediatric Dilated Cardiomyopathy
Amanda R Vicentino1, Anis Karimpour-Fard2, Taye Hamza3
1Department of Medicine, Division of Cardiology, University of Colorado Anschutz Medical Campus CO.
Insights
Biomarkers in pediatric dilated cardiomyopathy (DCM) can predict patient outcomes. Circulating miRNA and protein signatures show promise for early risk stratification in children with DCM.
Area of Science:
- Cardiology
- Genomics
- Proteomics
Background:
- Pediatric dilated cardiomyopathy (DCM) is a rare, progressive heart condition with unpredictable outcomes.
- Currently, there are no established prognostic biomarkers for children diagnosed with DCM.
- Identifying circulating biomarkers is crucial for tailoring patient management and predicting clinical trajectories.
Purpose of the Study:
- To identify circulating miRNA and protein signatures associated with clinical outcomes in pediatric DCM.
- To explore the predictive ability of these biomarkers for distinguishing between recovery and poor outcomes.
- To investigate the underlying biological pathways implicated in divergent clinical trajectories.
Main Methods:
- Serum samples from pediatric DCM patients were analyzed using RNA-seq for miRNA identification and SomaScan® for protein profiling.
- Machine learning methodologies were employed to assess the predictive power of identified circulating factors.
- Ingenuity Pathway Analysis was used to explore biological pathways associated with patient outcomes.
Main Results:
- Distinct miRNA and protein signatures differentiated between patients who recovered and those with poor outcomes (e.g., transplantation, mechanical support, death).
- Top candidate proteins (COL2A1, CXCL12, ADGRF5) and miRNAs (miR-874-3p, miR-335-3p, miR-323a-3p) showed strong discriminatory performance (AUC 0.92).
- Pathway analysis indicated that cardiac remodeling, fibrosis, and inflammatory signaling are key pathways differentiating patient outcomes.
Conclusions:
- Circulating miRNA and protein signatures at presentation can identify a molecular profile associated with divergent clinical trajectories in pediatric DCM.
- These multi-omic biomarkers show potential for early risk stratification in pediatric DCM patients.
- The findings provide insights into the mechanisms underlying divergent outcomes, supporting personalized management strategies.
Background:
Pediatric dilated cardiomyopathy (DCM) is a rare, progressive heart disease with variable outcomes that range from recovery to heart transplantation. To date, there are no prognostic biomarkers for children with DCM. Identifying circulating biomarkers that are associated with clinical outcomes is critical for personalized management.
Methods:
miRNAs were identified by RNA-seq, whereas proteins were identified by SomaScan®. Machine learning methodologies were used to explore the predictive ability of circulating factors identified from serum samples collected at the time of presentation with acute heart failure.
Results:
Thirty patients experienced poor outcomes (cardiac transplantation, mechanical circulatory support, or death) and 19 patients recovered left ventricular function. Distinct miRNA and protein signatures differentiated outcomes groups. Top candidate proteins (COL2A1, CXCL12, and ADGRF5) and miRNAs (miR-874-3p, miR-335-3p, miR-323a-3p) demonstrated strong discriminatory performance within the study cohort (recovered vs poor outcomes; Area Under the Curve of 0.92). Ingenuity Pathway Analysis implicates cardiac remodeling, fibrosis, and inflammatory signaling as central pathways differentiating patient outcomes.
Conclusions:
Circulating miRNA and protein signatures at presentation identify a circulating molecular signature associated with divergent clinical trajectories in pediatric DCM. These findings support the potential utility of multi-omic biomarkers for early risk stratification and provide insight into mechanisms underlying divergent outcomes.
