Project description: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.
Project description:The goal of this study is to identify circulating microRNAs with prognostic value in a large cohort of comatose survivors of out-of-hospital cardiac arrest. We performed RNA-Seq for short RNAs in plasma, collected 48 hours after return of spontaneous circulation, of 50 cardiac arrest patients including 25 good neurological outcome at 6 months (cerebral performance category 1) and 25 poor neurological outcome including death at 6 months (cerebral performance category score 5). The sequencing generated on average 18.5 million reads per sample. After mapping the reads and counting to relevant entries in miRBase 20, we found 236 microRNAs detected in all 50 samples with TPM above or equals to 1. 11 microRNAs were differentially expressed between 2 groups with False Discovery Rate (FDR) < 5%.
Project description:Prediction of neurological outcomes shortly after cardiac arrest would represent a major breakthrough. We tested the ability of gene expression profiles of blood cells to predict outcome in cardiac arrest patients.
Project description:Prediction of neurological outcomes shortly after cardiac arrest would represent a major breakthrough. We tested the ability of gene expression profiles of blood cells to predict outcome in cardiac arrest patients. 35 consecutive cardiac arrest patients treated with therapeutic hypothermia (33°C for 24h) were included in this prospective monocentre study. Cerebral Performance Category (CPC) was determined at discharge and 6 months later. All patients had blood sampling at the end of hypothermia. Gene expression profiles of blood cells were determined using 25,000~gene microarray in two groups of patients: good outcome (CPC 1-2) and bad outcome (CPC 3-5).
Project description:This pilot study aimed to investigate serum proteome profiles from unconscious patients admitted to hospital after out-of-hospital cardiac arrest according to temperature treatment and neurological outcome.
Project description:The consequences of cardiac arrest are often fatal, including brain injury after resuscitation. It has been reported that few people patients can recover to the neurological state before cardiac arrest. MiRNAs are short non-protein-coding RNA molecules that are evolutionarily conserved and ubiquitously expressed. Numerous pieces of research have reviewed the role of miRNAs in regulating neuronal apoptosis, regeneration, and plasticity of neurons, and inflammatory after cardiac arrest . As the stability of miRNAs in the bloodstream and the function in the regulation of neurological impairment after ischemia-reperfusion injury, microRNAs have been the most potential new biomarkers and therapeutic targets after cardiac arrest to alleviate neurological impairment . In this work, we found that the level of miR-483-5p is correlated to the prognosis of neurological function. To investigate the function of miR-483-5p on neurons after ischemia-reperfusion injury,we established highly differentiated PC12 cell lines in which miR-483-5p was overexpressed by transfection with miR-483-5p mimcis.We then performed gene expression profiling analysis using data obtained from RNA-seq of PC12 cells in different groups.
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.