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Circular RNAs to predict clinical outcome after cardiac arrest

Stefanizzi, Francesca M. ; Zhang, Lu ; Salgado-Somoza, Antonio ; Dankiewicz, Josef LU orcid ; Stammet, Pascal ; Hassager, Christian ; Wise, Matthew P. ; Friberg, Hans LU ; Cronberg, Tobias LU and Hundt, Alexander , et al. (2022) In Intensive Care Medicine Experimental 10(1).
Abstract

Background: Cardiac arrest (CA) represents the third leading cause of death worldwide. Among patients resuscitated and admitted to hospital, death and severe neurological sequelae are frequent but difficult to predict. Blood biomarkers offer clinicians the potential to improve prognostication. Previous studies suggest that circulating non-coding RNAs constitute a reservoir of novel biomarkers. Therefore, this study aims to identify circulating circular RNAs (circRNAs) associated with clinical outcome after CA. Results: Whole blood samples obtained 48 h after return of spontaneous circulation in 588 survivors from CA enrolled in the Target Temperature Management trial (TTM) were used in this study. Whole transcriptome RNA sequencing in 2... (More)

Background: Cardiac arrest (CA) represents the third leading cause of death worldwide. Among patients resuscitated and admitted to hospital, death and severe neurological sequelae are frequent but difficult to predict. Blood biomarkers offer clinicians the potential to improve prognostication. Previous studies suggest that circulating non-coding RNAs constitute a reservoir of novel biomarkers. Therefore, this study aims to identify circulating circular RNAs (circRNAs) associated with clinical outcome after CA. Results: Whole blood samples obtained 48 h after return of spontaneous circulation in 588 survivors from CA enrolled in the Target Temperature Management trial (TTM) were used in this study. Whole transcriptome RNA sequencing in 2 groups of 23 sex-matched patients identified 28 circRNAs associated with neurological outcome and survival. The circRNA circNFAT5 was selected for further analysis using quantitative PCR. In the TTM-trial (n = 542), circNFAT5 was upregulated in patients with poor outcome as compared to patients with good neurological outcome (p < 0.001). This increase was independent of TTM regimen and sex. The adjusted odds ratio of circNFAT5 to predict neurological outcome was 1.39 [1.07–1.83] (OR [95% confidence interval]). CircNFAT5 predicted 6-month survival with an adjusted hazard ratio of 1.31 [1.13–1.52]. Conclusion: We identified circulating circRNAs associated with clinical outcome after CA, among which circNFAT5 may have potential to aid in predicting neurological outcome and survival when used in combination with established biomarkers of CA.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Biomarkers, Circular RNAs, Out-of-hospital cardiac arrest, Prognostication
in
Intensive Care Medicine Experimental
volume
10
issue
1
article number
41
publisher
Springer
external identifiers
  • scopus:85140876990
  • pmid:36303007
ISSN
2197-425X
DOI
10.1186/s40635-022-00470-7
language
English
LU publication?
yes
id
0722288d-8a79-4628-baec-07c34f7108ee
date added to LUP
2022-12-06 12:21:30
date last changed
2024-04-18 17:55:24
@article{0722288d-8a79-4628-baec-07c34f7108ee,
  abstract     = {{<p>Background: Cardiac arrest (CA) represents the third leading cause of death worldwide. Among patients resuscitated and admitted to hospital, death and severe neurological sequelae are frequent but difficult to predict. Blood biomarkers offer clinicians the potential to improve prognostication. Previous studies suggest that circulating non-coding RNAs constitute a reservoir of novel biomarkers. Therefore, this study aims to identify circulating circular RNAs (circRNAs) associated with clinical outcome after CA. Results: Whole blood samples obtained 48 h after return of spontaneous circulation in 588 survivors from CA enrolled in the Target Temperature Management trial (TTM) were used in this study. Whole transcriptome RNA sequencing in 2 groups of 23 sex-matched patients identified 28 circRNAs associated with neurological outcome and survival. The circRNA circNFAT5 was selected for further analysis using quantitative PCR. In the TTM-trial (n = 542), circNFAT5 was upregulated in patients with poor outcome as compared to patients with good neurological outcome (p &lt; 0.001). This increase was independent of TTM regimen and sex. The adjusted odds ratio of circNFAT5 to predict neurological outcome was 1.39 [1.07–1.83] (OR [95% confidence interval]). CircNFAT5 predicted 6-month survival with an adjusted hazard ratio of 1.31 [1.13–1.52]. Conclusion: We identified circulating circRNAs associated with clinical outcome after CA, among which circNFAT5 may have potential to aid in predicting neurological outcome and survival when used in combination with established biomarkers of CA.</p>}},
  author       = {{Stefanizzi, Francesca M. and Zhang, Lu and Salgado-Somoza, Antonio and Dankiewicz, Josef and Stammet, Pascal and Hassager, Christian and Wise, Matthew P. and Friberg, Hans and Cronberg, Tobias and Hundt, Alexander and Kjaergaard, Jesper and Nielsen, Niklas and Devaux, Yvan}},
  issn         = {{2197-425X}},
  keywords     = {{Biomarkers; Circular RNAs; Out-of-hospital cardiac arrest; Prognostication}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{Springer}},
  series       = {{Intensive Care Medicine Experimental}},
  title        = {{Circular RNAs to predict clinical outcome after cardiac arrest}},
  url          = {{http://dx.doi.org/10.1186/s40635-022-00470-7}},
  doi          = {{10.1186/s40635-022-00470-7}},
  volume       = {{10}},
  year         = {{2022}},
}