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Published in: Translational Stroke Research 3/2020

01-06-2020 | Stroke | Original Article

Cardioembolic Ischemic Stroke Gene Expression Fingerprint in Blood: a Systematic Review and Verification Analysis

Authors: Teresa García-Berrocoso, Elena Palà, Marta Consegal, Benedetta Piccardi, Alex Negro, Natalia Gill, Anna Penalba, Hector Huerga Encabo, Israel Fernández-Cadenas, Andreas Meisel, Christian Meisel, Glen C. Jickling, Miguel Ángel Muñoz, Josep Lluis Clúa-Espuny, Alonso Pedrote, Jorge Pagola, Jesús Juega, Alejandro Bustamante, Joan Montaner

Published in: Translational Stroke Research | Issue 3/2020

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Abstract

An accurate etiological classification is key to optimize secondary prevention after ischemic stroke, but the cause remains undetermined in one third of patients. Several studies pointed out the usefulness of circulating gene expression markers to discriminate cardioembolic (CE) strokes, mainly due to atrial fibrillation (AF), while only exploring them in small cohorts. A systematic review of studies analyzing high-throughput gene expression in blood samples to discriminate CE strokes was performed. Significantly dysregulated genes were considered as candidates, and a selection of them was validated by RT-qPCR in 100 patients with defined CE or atherothrombotic (LAA) stroke etiology. Longitudinal performance was evaluated in 12 patients at three time points. Their usefulness as biomarkers for AF was tested in 120 cryptogenic strokes and 100 individuals at high-risk for stroke. Three published studies plus three unpublished datasets were considered for candidate selection. Sixty-seven genes were found dysregulated in CE strokes. CREM, PELI1, and ZAK were verified to be up-regulated in CE vs LAA (p = 0.010, p = 0.003, p < 0.001, respectively), without changes in their expression within the first 24 h after stroke onset. The combined up-regulation of these three biomarkers increased the probability of suffering from CE stroke by 23-fold. In cryptogenic strokes with subsequent AF detection, PELI1 and CREM showed overexpression (p = 0.017, p = 0.059, respectively), whereas in high-risk asymptomatic populations, all three genes showed potential to detect AF (p = 0.007, p = 0.007, p = 0.015). The proved discriminatory capacity of these gene expression markers to detect cardioembolism even in cryptogenic strokes and asymptomatic high-risk populations might bring up their use as biomarkers.
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Metadata
Title
Cardioembolic Ischemic Stroke Gene Expression Fingerprint in Blood: a Systematic Review and Verification Analysis
Authors
Teresa García-Berrocoso
Elena Palà
Marta Consegal
Benedetta Piccardi
Alex Negro
Natalia Gill
Anna Penalba
Hector Huerga Encabo
Israel Fernández-Cadenas
Andreas Meisel
Christian Meisel
Glen C. Jickling
Miguel Ángel Muñoz
Josep Lluis Clúa-Espuny
Alonso Pedrote
Jorge Pagola
Jesús Juega
Alejandro Bustamante
Joan Montaner
Publication date
01-06-2020
Publisher
Springer US
Published in
Translational Stroke Research / Issue 3/2020
Print ISSN: 1868-4483
Electronic ISSN: 1868-601X
DOI
https://doi.org/10.1007/s12975-019-00730-x

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