Related Experiment Videos
Early blood transcriptomic signature predicts patients' outcome after out-of-hospital cardiac arrest
Renaud Tissier1, Hakim Hocini2, Nicolas Tchitchek3
1Inserm, U955, F94000, Créteil, France; Université Paris Est, UMR_S955, UPEC, Ecole Nationale Vétérinaire d'Alfort, F-94000, Créteil, France.
Insights
A novel gene expression signature in blood can predict neurological outcomes in out-of-hospital cardiac arrest (OHCA) survivors. This immune response balance offers early prognostic insights for OHCA patients.
Area of Science:
- * Transcriptomics and immunology
- * Clinical outcomes research
Background:
- * Early prognostication after out-of-hospital cardiac arrest (OHCA) is clinically challenging.
- * Identifying reliable prognostic markers is crucial for patient management and treatment strategies.
Purpose of the Study:
- * To investigate genome-wide blood gene expression for novel prognostic tools in OHCA survivors.
- * To identify transcriptomic signatures associated with neurological outcomes post-OHCA.
Main Methods:
- * Gene expression profiling of blood samples from 69 OHCA survivors using Illumina HumanHT-12 V4 BeadChip.
- * Analysis of transcriptomic differences between patients with favorable (cerebral performance category [CPC] 1-2) and unfavorable (CPC > 2) neurological outcomes at 60 days.
- * Differential expression, functional enrichment, and upstream regulator analyses were performed.
Main Results:
- * A distinct transcriptomic signature of 76 genes at Day 0 and Day 1 post-resuscitation differentiated neurological outcomes.
- * This signature showed a down-regulation of adaptive immunity and up-regulation of innate immunity and inflammation in unfavorable outcome patients.
- * Logistic regression models incorporating these genes accurately predicted clinical outcomes (88% specificity, 83% hit rate).
Conclusions:
- * A blood-based transcriptomic signature reflecting immune response balance can predict neurological outcomes early after OHCA.
- * This finding highlights the potential of immune system dynamics as a prognostic indicator in OHCA.
- * Further validation in larger patient cohorts is warranted.
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 neurological 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.