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Circular RNAs to predict clinical outcome after cardiac arrest

ABSTRACT: Background: Cardiac arrest (CA) represents the third leading cause of death worldwide. Among survivors, severe neurological sequelae are frequent but difficult to predict. Novel prognostic biomarkers would offer clinicians the possibility to deliver personalized healthcare. The potential of small circulating noncoding RNAs (microRNAs) to predict neurological outcome and survival after CA has been reported. Objective: This study aims to identify circulating circular RNAs (circRNAs) associated with clinical outcome after CA. Methods and Results: Methods and Results: Whole blood samples obtained 48h after return of spontaneous circulation from 23 sex-matched survivors and 23 deceased cardiac arrest (CA) patients were enrolled in this study. Whole transcriptome RNA sequencing identified candidate RNAs associated with neurological outcome and survival. Conclusion: We have identified candidate RNAs associated with clinical outcome after CA whose predictive value remains to be confirmed in large populations.

ORGANISM(S): Homo sapiens

PROVIDER: GSE197764 | GEO | 2022/11/02

REPOSITORIES: GEO

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Project description:Background: Early prognostication is a major challenge after out-of-hospital cardiac arrest (OHCA). Aims: We hypothesized that a genome-wide analysis of blood gene expression could offer new prognostic tools and lines of research. Methods: Sixty-nine patients were enrolled from an ancillary study of the clinical trial NCT00999583 that tested the effect of erythropoietin (EPO) after OHCA. Blood samples were collected in comatose survivors of OHCA at hospital admission and 1 and 3 days after resuscitation. Gene expression profiles were analyzed (Illumina HumanHT-12 V4 BeadChip; >34,000 genes). Patients were classified into two categories representing neurologically favorable outcome (Cerebral Performance Category [CPC] = 1-2) vs unfavorable outcome (CPC>2) at Day 60 after OHCA. Differential and functional enrichment analyses were performed to compare transcriptomic profiles between these two categories. Results: Among the 69 enrolled patients, 33 and 36 patients were treated or not by EPO, respectively. Among them, 42% had a favorable neurological outcome in both groups. EPO did not affect the transcriptomic response at Day-0 and 1 after OHCA. In contrast, 76 transcripts differed at Day-0 between patients with unfavorable vs favorable neurological outcome. This signature persisted at Day-1 after OHCA. Functional enrichment analysis revealed a down-regulation of adaptive immunity with concomitant up-regulation of innate immunity and inflammation in patients with unfavorable vs favorable neurological outcome. The transcription of many genes of the HLA family was decreased in patients with unfavorable vs favorable neurological outcome. Concomitantly, neutrophil activation and inflammation were observed. Up-stream regulators analysis showed the implication of numerous factors involved in cell cycle and damages. A logistic regression including a set of genes allowed a reliable prediction of the clinical outcomes (Specificity=88%; Hit Rate=83%). Conclusions: A transcriptomic signature involving a counterbalance between adaptive and innate immune responses is able to predict neurological outcome very early after hospital admission after OHCA. This deserves confirmation in a larger population.

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Circular RNAs to predict clinical outcome after cardiac arrest

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