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Published on: April 14, 2023
MicroRNA and Inflammatory Biomarker Signatures Associated With Neurological Outcome After Out-Of-Hospital Cardiac
Francisco Rafael Jiménez-Trinidad1,2,3, Eva Moreno-Monterde1,4,5, Carlos Roca-Guerrero1,4,5
1Fundació Clinic Per la Recerca Biomèdica, Institute d'Investigacions Biomèdiques August Pi i Sunyer (FCRB-IDIBAPS), Barcelona, Spain.
Background:
Early neuroprognostication in Out-of-Hospital Cardiac Arrest (OHCA) remains challenging due to the lack of reliable biomarkers. Circulating microRNAs have emerged as potential indicators of inflammation and brain injury (HIBI). This study aimed to evaluate whether in silico-predicted microRNAs could discriminate neurological outcomes early in OHCA patients.
Methods:
Consecutive OHCA patients admitted to the Acute Cardiac Care Unit with available cryopreserved blood samples were analysed. Neurological outcome was classified into favourable (Cerebral Performance Category (CPC) 1-2) and unfavourable (CPC 3-5). Blood samples at 0, 24, 72 h after hospital admission were collected. An in silico-derived network of inflammation-HIBI-related microRNA was generated and validated in all patients at the three time-points.
Results:
A total of 100 patients were included (59.7 ± 12.5 years, 19% women). 53% had unfavourable neurological outcomes. Eleven candidate microRNAs were identified, showing differential time-dependent expression within 72 h. The earlier and most predictive microRNAs for unfavourable neurological outcome were miR-1-3p (AUC 0.637) and miR-124-3p (AUC 0.606) at 0 h, miR-21-5p (AUC 0.614) and miR-499a-5p (AUC 0.645) at 24 h. The miR-499-5p maintained the best AUC across all time-points. A multiparametric model achieved an AUC of 0.690. A pro-inflammatory environment, characterised by C-Reactive Protein (CRP) and neutrophil-to-lymphocyte ratio, showed distinct temporal expression patterns regarding neurological outcome. Neuroinflammatory miR-let-7a-5p, miR-23a-3p and miR-146a-5p were significantly overexpressed in the unfavourable group and correlated positively with CRP.
Conclusions:
In silico derived inflammatory and HIBI-related microRNAs showed time-dependent expression patterns that may distinguish neurological outcomes within 72 h after OHCA.
