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Postoperative Organ Dysfunction Risk Stratification Using Extracellular Vesicle-Derived circRNAs in Pediatric
Fahd Alhamdan1,2,3, Koichi Yuki1,2,3
1Department of Anesthesiology, Critical Care and Pain Medicine, Cardiac Anesthesia Division, Boston Children's Hospital, Boston, MA 02115, USA.
Insights
Investigating circular RNAs in extracellular vesicles after congenital heart defect surgery reveals potential biomarkers for organ dysfunction in infants. These findings may improve post-surgical management and guide new therapies.
Area of Science:
- Biochemistry
- Pediatric Surgery
- Molecular Biology
Background:
- Congenital heart disease (CHD) surgery outcomes have improved, yet post-operative organ dysfunction remains a challenge, especially in neonates and infants.
- Research is needed to identify reliable biomarkers for predicting and managing post-surgical organ dysfunction in pediatric patients.
Purpose of the Study:
- To investigate the role of circular RNAs (circRNAs) in plasma-derived extracellular vesicles (EVs) as potential biomarkers for post-surgical organ dysfunction in neonates and infants with CHD.
- To identify specific circRNAs that correlate with organ dysfunction severity and predict outcomes.
Main Methods:
- Analysis of plasma-derived extracellular vesicle (EV) circRNAs in neonates and infants undergoing CHD surgery.
- Comparison of circRNA expression profiles between patients with and without post-surgical organ dysfunction (OD).
- Correlation analysis of circRNA levels with the Pediatric Logistic Organ Dysfunction (PELOD) score.
Main Results:
- Significant changes in EV circRNA expression were observed post-surgery in the organ dysfunction group compared to controls.
- Tissue injury-related pathways were implicated in organ dysfunction.
- Five specific circRNAs (circ-CELSR1, circ-PLXNA1, circ-OBSL1, circ-DAB2IP, circ-KANK1) showed significant correlation with PELOD score.
- These five circRNAs demonstrated high diagnostic performance (AUC = 0.95) for predicting organ dysfunction.
Conclusions:
- Plasma-derived EV circRNAs are promising prognostic markers for post-surgical organ dysfunction in infants with CHD.
- These biomarkers could aid in early detection, management, and therapeutic strategy development for pediatric patients undergoing cardiac surgery.
Abstract:
Breakthroughs in surgical and medical techniques have significantly improved outcomes for children with congenital heart disease (CHD), but research continues to address the ongoing challenge of organ dysfunction after surgery, particularly in neonates and infants. Our study explored circular RNAs (circRNAs) within plasma-derived extracellular vesicles (EVs) in neonates and infants undergoing CHD surgery. Post-surgery EV circRNAs showed dramatic expression changes between organ dysfunction (OD) and control groups. Tissue injury-related pathways were consistent across pre- and post-surgery in OD. The top two significant predicted tissue sources of these circRNAs originated from the respiratory system, aligning with the fact that all patients in the OD arm experienced respiratory dysfunction. Five of these circRNAs, namely circ-CELSR1, circ-PLXNA1, circ-OBSL1, circ-DAB2IP, and circ-KANK1, significantly correlated with PELOD (Pediatric Logistic Organ Dysfunction) score and demonstrated high performance (AUC = 0.95), supporting the potential of circRNAs as prognostic markers. These findings pave the way for EV circRNAs as promising tools for managing post-surgical organ dysfunction and potentially guiding therapeutic strategies in children with CHD.
