Extracellular microRNAs in blood differentiate between ischaemic and haemorrhagic stroke subtypes

Rapid identification of patients suffering from cerebral ischaemia, while excluding intracerebral haemorrhage, can assist with patient triage and expand patient access to chemical and mechanical revascularization. We sought to identify blood-based, extracellular microRNAs 15 (ex-miRNAs) derived from...

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Published inJournal of extracellular vesicles Vol. 9; no. 1; pp. 1713540 - n/a
Main Authors Kalani, M. Yashar S., Alsop, Eric, Meechoovet, Bessie, Beecroft, Taylor, Agrawal, Komal, Whitsett, Timothy G., Huentelman, Matthew J., Spetzler, Robert F., Nakaji, Peter, Kim, Seungchan, Van Keuren-Jensen, Kendall
Format Journal Article
LanguageEnglish
Published Sweden Taylor & Francis 01.01.2020
John Wiley & Sons, Inc
Wiley
Subjects
Aneurysm
biomarker
Biomarkers
Blood
Cerebral blood flow
Disease
extracellular microRNA (ex-miRNA)
Extracellular vesicles
Hemorrhage
Intraparenchymal haemorrhage (IPH)
ischaemic stroke
Ischemia
large vessel occlusion (LVO)
MicroRNAs
miRNA
Patients
Plasma
Stroke
subarachnoid haemorrhage (SAH)
Subarachnoid hemorrhage
ischaemic stroke
large vessel occlusion (LVO)
biomarker
Intraparenchymal haemorrhage (IPH)
extracellular microRNA (ex-miRNA)
subarachnoid haemorrhage (SAH)
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Abstract Rapid identification of patients suffering from cerebral ischaemia, while excluding intracerebral haemorrhage, can assist with patient triage and expand patient access to chemical and mechanical revascularization. We sought to identify blood-based, extracellular microRNAs 15 (ex-miRNAs) derived from extracellular vesicles associated with major stroke subtypes using clinical samples from subjects with spontaneous intraparenchymal haemorrhage (IPH), aneurysmal subarachnoid haemorrhage (SAH) and ischaemic stroke due to cerebral vessel occlusion. We collected blood from patients presenting with IPH (n = 19), SAH (n = 17) and ischaemic stroke (n = 21). We isolated extracellular vesicles from plasma, extracted RNA cargo, 20 sequenced the small RNAs and performed bioinformatic analyses to identify ex-miRNA biomarkers predictive of the stroke subtypes. Sixty-seven miRNAs were significantly variant across the stroke subtypes. A subset of exmiRNAs differed between haemorrhagic and ischaemic strokes, and LASSO analysis could distinguish SAH from the other subtypes with an accuracy of 0.972 ± 0.002. Further analyses predicted 25 miRNA classifiers that stratify IPH from ischaemic stroke with an accuracy of 0.811 ± 0.004 and distinguish haemorrhagic from ischaemic stroke with an accuracy of 0.813 ± 0.003. Blood-based, ex-miRNAs have predictive value, and could be capable of distinguishing between major stroke subtypes with refinement and validation. Such a biomarker could one day aid in the triage of patients to expand the pool eligible for effective treatment.
AbstractList Rapid identification of patients suffering from cerebral ischaemia, while excluding intracerebral haemorrhage, can assist with patient triage and expand patient access to chemical and mechanical revascularization. We sought to identify blood-based, extracellular microRNAs 15 (ex-miRNAs) derived from extracellular vesicles associated with major stroke subtypes using clinical samples from subjects with spontaneous intraparenchymal haemorrhage (IPH), aneurysmal subarachnoid haemorrhage (SAH) and ischaemic stroke due to cerebral vessel occlusion. We collected blood from patients presenting with IPH (n = 19), SAH (n = 17) and ischaemic stroke (n = 21). We isolated extracellular vesicles from plasma, extracted RNA cargo, 20 sequenced the small RNAs and performed bioinformatic analyses to identify ex-miRNA biomarkers predictive of the stroke subtypes. Sixty-seven miRNAs were significantly variant across the stroke subtypes. A subset of exmiRNAs differed between haemorrhagic and ischaemic strokes, and LASSO analysis could distinguish SAH from the other subtypes with an accuracy of 0.972 ± 0.002. Further analyses predicted 25 miRNA classifiers that stratify IPH from ischaemic stroke with an accuracy of 0.811 ± 0.004 and distinguish haemorrhagic from ischaemic stroke with an accuracy of 0.813 ± 0.003. Blood-based, ex-miRNAs have predictive value, and could be capable of distinguishing between major stroke subtypes with refinement and validation. Such a biomarker could one day aid in the triage of patients to expand the pool eligible for effective treatment.
Rapid identification of patients suffering from cerebral ischaemia, while excluding intracerebral haemorrhage, can assist with patient triage and expand patient access to chemical and mechanical revascularization. We sought to identify blood-based, extracellular microRNAs 15 (ex-miRNAs) derived from extracellular vesicles associated with major stroke subtypes using clinical samples from subjects with spontaneous intraparenchymal haemorrhage (IPH), aneurysmal subarachnoid haemorrhage (SAH) and ischaemic stroke due to cerebral vessel occlusion. We collected blood from patients presenting with IPH (n = 19), SAH (n = 17) and ischaemic stroke (n = 21). We isolated extracellular vesicles from plasma, extracted RNA cargo, 20 sequenced the small RNAs and performed bioinformatic analyses to identify ex-miRNA biomarkers predictive of the stroke subtypes. Sixty-seven miRNAs were significantly variant across the stroke subtypes. A subset of exmiRNAs differed between haemorrhagic and ischaemic strokes, and LASSO analysis could distinguish SAH from the other subtypes with an accuracy of 0.972 ± 0.002. Further analyses predicted 25 miRNA classifiers that stratify IPH from ischaemic stroke with an accuracy of 0.811 ± 0.004 and distinguish haemorrhagic from ischaemic stroke with an accuracy of 0.813 ± 0.003. Blood-based, ex-miRNAs have predictive value, and could be capable of distinguishing between major stroke subtypes with refinement and validation. Such a biomarker could one day aid in the triage of patients to expand the pool eligible for effective treatment.Rapid identification of patients suffering from cerebral ischaemia, while excluding intracerebral haemorrhage, can assist with patient triage and expand patient access to chemical and mechanical revascularization. We sought to identify blood-based, extracellular microRNAs 15 (ex-miRNAs) derived from extracellular vesicles associated with major stroke subtypes using clinical samples from subjects with spontaneous intraparenchymal haemorrhage (IPH), aneurysmal subarachnoid haemorrhage (SAH) and ischaemic stroke due to cerebral vessel occlusion. We collected blood from patients presenting with IPH (n = 19), SAH (n = 17) and ischaemic stroke (n = 21). We isolated extracellular vesicles from plasma, extracted RNA cargo, 20 sequenced the small RNAs and performed bioinformatic analyses to identify ex-miRNA biomarkers predictive of the stroke subtypes. Sixty-seven miRNAs were significantly variant across the stroke subtypes. A subset of exmiRNAs differed between haemorrhagic and ischaemic strokes, and LASSO analysis could distinguish SAH from the other subtypes with an accuracy of 0.972 ± 0.002. Further analyses predicted 25 miRNA classifiers that stratify IPH from ischaemic stroke with an accuracy of 0.811 ± 0.004 and distinguish haemorrhagic from ischaemic stroke with an accuracy of 0.813 ± 0.003. Blood-based, ex-miRNAs have predictive value, and could be capable of distinguishing between major stroke subtypes with refinement and validation. Such a biomarker could one day aid in the triage of patients to expand the pool eligible for effective treatment.
ABSTRACT Rapid identification of patients suffering from cerebral ischaemia, while excluding intracerebral haemorrhage, can assist with patient triage and expand patient access to chemical and mechanical revascularization. We sought to identify blood‐based, extracellular microRNAs 15 (ex‐miRNAs) derived from extracellular vesicles associated with major stroke subtypes using clinical samples from subjects with spontaneous intraparenchymal haemorrhage (IPH), aneurysmal subarachnoid haemorrhage (SAH) and ischaemic stroke due to cerebral vessel occlusion. We collected blood from patients presenting with IPH (n = 19), SAH (n = 17) and ischaemic stroke (n = 21). We isolated extracellular vesicles from plasma, extracted RNA cargo, 20 sequenced the small RNAs and performed bioinformatic analyses to identify ex‐miRNA biomarkers predictive of the stroke subtypes. Sixty‐seven miRNAs were significantly variant across the stroke subtypes. A subset of exmiRNAs differed between haemorrhagic and ischaemic strokes, and LASSO analysis could distinguish SAH from the other subtypes with an accuracy of 0.972 ± 0.002. Further analyses predicted 25 miRNA classifiers that stratify IPH from ischaemic stroke with an accuracy of 0.811 ± 0.004 and distinguish haemorrhagic from ischaemic stroke with an accuracy of 0.813 ± 0.003. Blood‐based, ex‐miRNAs have predictive value, and could be capable of distinguishing between major stroke subtypes with refinement and validation. Such a biomarker could one day aid in the triage of patients to expand the pool eligible for effective treatment.
Rapid identification of patients suffering from cerebral ischaemia, while excluding intracerebral haemorrhage, can assist with patient triage and expand patient access to chemical and mechanical revascularization. We sought to identify blood‐based, extracellular microRNAs 15 (ex‐miRNAs) derived from extracellular vesicles associated with major stroke subtypes using clinical samples from subjects with spontaneous intraparenchymal haemorrhage (IPH), aneurysmal subarachnoid haemorrhage (SAH) and ischaemic stroke due to cerebral vessel occlusion. We collected blood from patients presenting with IPH (n = 19), SAH (n = 17) and ischaemic stroke (n = 21). We isolated extracellular vesicles from plasma, extracted RNA cargo, 20 sequenced the small RNAs and performed bioinformatic analyses to identify ex‐miRNA biomarkers predictive of the stroke subtypes. Sixty‐seven miRNAs were significantly variant across the stroke subtypes. A subset of exmiRNAs differed between haemorrhagic and ischaemic strokes, and LASSO analysis could distinguish SAH from the other subtypes with an accuracy of 0.972 ± 0.002. Further analyses predicted 25 miRNA classifiers that stratify IPH from ischaemic stroke with an accuracy of 0.811 ± 0.004 and distinguish haemorrhagic from ischaemic stroke with an accuracy of 0.813 ± 0.003. Blood‐based, ex‐miRNAs have predictive value, and could be capable of distinguishing between major stroke subtypes with refinement and validation. Such a biomarker could one day aid in the triage of patients to expand the pool eligible for effective treatment.
ABSTRACT Rapid identification of patients suffering from cerebral ischaemia, while excluding intracerebral haemorrhage, can assist with patient triage and expand patient access to chemical and mechanical revascularization. We sought to identify blood‐based, extracellular microRNAs 15 (ex‐miRNAs) derived from extracellular vesicles associated with major stroke subtypes using clinical samples from subjects with spontaneous intraparenchymal haemorrhage (IPH), aneurysmal subarachnoid haemorrhage (SAH) and ischaemic stroke due to cerebral vessel occlusion. We collected blood from patients presenting with IPH (n = 19), SAH (n = 17) and ischaemic stroke (n = 21). We isolated extracellular vesicles from plasma, extracted RNA cargo, 20 sequenced the small RNAs and performed bioinformatic analyses to identify ex‐miRNA biomarkers predictive of the stroke subtypes. Sixty‐seven miRNAs were significantly variant across the stroke subtypes. A subset of exmiRNAs differed between haemorrhagic and ischaemic strokes, and LASSO analysis could distinguish SAH from the other subtypes with an accuracy of 0.972 ± 0.002. Further analyses predicted 25 miRNA classifiers that stratify IPH from ischaemic stroke with an accuracy of 0.811 ± 0.004 and distinguish haemorrhagic from ischaemic stroke with an accuracy of 0.813 ± 0.003. Blood‐based, ex‐miRNAs have predictive value, and could be capable of distinguishing between major stroke subtypes with refinement and validation. Such a biomarker could one day aid in the triage of patients to expand the pool eligible for effective treatment.
Author Alsop, Eric
Meechoovet, Bessie
Kalani, M. Yashar S.
Beecroft, Taylor
Whitsett, Timothy G.
Spetzler, Robert F.
Van Keuren-Jensen, Kendall
Huentelman, Matthew J.
Nakaji, Peter
Agrawal, Komal
Kim, Seungchan
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  organization: University of Virginia School of Medicine
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Copyright 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group on behalf of The International Society for Extracellular Vesicles. 2020
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2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group on behalf of The International Society for Extracellular Vesicles. 2020 The Author(s)
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Issue 1
Keywords ischaemic stroke
large vessel occlusion (LVO)
biomarker
Intraparenchymal haemorrhage (IPH)
extracellular microRNA (ex-miRNA)
subarachnoid haemorrhage (SAH)
Language English
License open-access: http://creativecommons.org/licenses/by-nc/4.0/: http://creativecommons.org/licenses/by-nc/4.0/: This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
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2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group on behalf of The International Society for Extracellular Vesicles.
This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
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Notes These authors contributed equally to this work
Currently: University of Oxford, Park End Street, Oxford, OX1 1HP, UK
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– name: John Wiley & Sons, Inc
– name: Wiley
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Snippet Rapid identification of patients suffering from cerebral ischaemia, while excluding intracerebral haemorrhage, can assist with patient triage and expand...
ABSTRACT Rapid identification of patients suffering from cerebral ischaemia, while excluding intracerebral haemorrhage, can assist with patient triage and...
ABSTRACT Rapid identification of patients suffering from cerebral ischaemia, while excluding intracerebral haemorrhage, can assist with patient triage and...
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StartPage 1713540
SubjectTerms Aneurysm
biomarker
Biomarkers
Blood
Cerebral blood flow
Disease
extracellular microRNA (ex-miRNA)
Extracellular vesicles
Hemorrhage
Intraparenchymal haemorrhage (IPH)
ischaemic stroke
Ischemia
large vessel occlusion (LVO)
MicroRNAs
miRNA
Patients
Plasma
Stroke
subarachnoid haemorrhage (SAH)
Subarachnoid hemorrhage
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Title Extracellular microRNAs in blood differentiate between ischaemic and haemorrhagic stroke subtypes
URI https://www.tandfonline.com/doi/abs/10.1080/20013078.2020.1713540
https://onlinelibrary.wiley.com/doi/abs/10.1080%2F20013078.2020.1713540
https://www.ncbi.nlm.nih.gov/pubmed/32128071
https://www.proquest.com/docview/3092345200
https://www.proquest.com/docview/2371143505
https://pubmed.ncbi.nlm.nih.gov/PMC7034450
https://doaj.org/article/df28f35c2c89457d889a105785da6713
Volume 9
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