Francesca Maria STEFANIZZI

Circular RNAs to predict outcome after out-of-hospital cardiac arrest
More than 400,000 cases of cardiac arrest (CA) occur each year in Europe. Among patients admitted to intensive care unit, the mortality rate averages 50%. Accurate prediction of outcomes would enable health care adaptation. Therefore, the discovery of new specific biomarkers could improve the prognosis of these patients. Cumulative evidence suggests circulating circular RNAs (circRNAs) as reservoirs of new biomarkers.
The goal of this project is to identify circulating circRNAs able of predicting the outcome of patients after CA.
Whole blood samples were collected from patients of the Target Temperature Management trial (TTM-trial; NCT01020916) 48h after CA in PAXgene RNA tubes. RNA sequencing was performed in a subgroup of 46 patients half of which survived with no major neurological sequelae (cerebral performance category score 1 – CPC1) and the other half died within 6 months (CPC5). The expression levels of the candidate circRNAs were measured by qRT-PCR in the entire cohort of the TTM-trial (n=542). The ability of circRNAs to predict neurological outcome was assessed using logistic regression while survival analyses were performed using Kaplan-Meier curves and Cox proportional hazards.
Twenty-seven circRNAs were differentially expressed among the patients with CPC1 and CPC5 with a p-value <0.05 and fold-change ≥ 1.5. The circularity of eight circRNAs was confirmed and the selected candidates were measured in the entire TTM-trial through qRT-PCR. Among these, one circRNA named circ01 seem to predict neurological outcome with an odds ratio (OR) +/- 95% confidence interval (CI) of 1.4 [1.1-1.6] and survival with a hazards ratio of 1.3 [1.1-1.5]. The prediction was preserved after adjustment with demographic and clinical parameters. Patients with high levels of circ01 were associated with a lower chance of survival.
Circulating levels of circ01 measured 48h after OHCA are associated with poor neurological outcome and survival.

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