Identification of Novel Circulating miRNAs in Patients with Acute Ischemic Stroke

<div><p>Ischemic strokes are associated with significant morbidity and mortality, but currently there are no reliable prognostic or diagnostic blood biomarkers. MicroRNAs (miRNAs) regulate various molecular pathways and may be used as biomarkers. Using RNA-Seq, we conducted comprehensive...

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Main Author: Eman K. Aldous (13914057) (author)
Other Authors: Salman M. Toor (8854751) (author), Aijaz Parray (290256) (author), Yasser Al-Sarraj (11721425) (author), Ilhame Diboun (3522413) (author), Essam M. Abdelalim (5768072) (author), Abdelilah Arredouani (10914455) (author), Omar El-Agnaf (2134222) (author), Paul J. Thornalley (291723) (author), Naveed Akhtar (4919398) (author), Sajitha V. Pananchikkal (13914060) (author), Ashfaq Shuaib (4919407) (author), Nehad M. Alajez (7397276) (author), Omar M. E. Albagha (11704871) (author)
Published: 2022
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author Eman K. Aldous (13914057)
author2 Salman M. Toor (8854751)
Aijaz Parray (290256)
Yasser Al-Sarraj (11721425)
Ilhame Diboun (3522413)
Essam M. Abdelalim (5768072)
Abdelilah Arredouani (10914455)
Omar El-Agnaf (2134222)
Paul J. Thornalley (291723)
Naveed Akhtar (4919398)
Sajitha V. Pananchikkal (13914060)
Ashfaq Shuaib (4919407)
Nehad M. Alajez (7397276)
Omar M. E. Albagha (11704871)
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author_facet Eman K. Aldous (13914057)
Salman M. Toor (8854751)
Aijaz Parray (290256)
Yasser Al-Sarraj (11721425)
Ilhame Diboun (3522413)
Essam M. Abdelalim (5768072)
Abdelilah Arredouani (10914455)
Omar El-Agnaf (2134222)
Paul J. Thornalley (291723)
Naveed Akhtar (4919398)
Sajitha V. Pananchikkal (13914060)
Ashfaq Shuaib (4919407)
Nehad M. Alajez (7397276)
Omar M. E. Albagha (11704871)
author_role author
dc.creator.none.fl_str_mv Eman K. Aldous (13914057)
Salman M. Toor (8854751)
Aijaz Parray (290256)
Yasser Al-Sarraj (11721425)
Ilhame Diboun (3522413)
Essam M. Abdelalim (5768072)
Abdelilah Arredouani (10914455)
Omar El-Agnaf (2134222)
Paul J. Thornalley (291723)
Naveed Akhtar (4919398)
Sajitha V. Pananchikkal (13914060)
Ashfaq Shuaib (4919407)
Nehad M. Alajez (7397276)
Omar M. E. Albagha (11704871)
dc.date.none.fl_str_mv 2022-03-21T03:00:00Z
dc.identifier.none.fl_str_mv 10.3390/ijms23063387
dc.relation.none.fl_str_mv https://figshare.com/articles/journal_contribution/Identification_of_Novel_Circulating_miRNAs_in_Patients_with_Acute_Ischemic_Stroke/25679838
dc.rights.none.fl_str_mv CC BY 4.0
info:eu-repo/semantics/openAccess
dc.subject.none.fl_str_mv Biomedical and clinical sciences
Clinical sciences
Neurosciences
microRNA
miRNA
ischemic stroke
biomarkers
dc.title.none.fl_str_mv Identification of Novel Circulating miRNAs in Patients with Acute Ischemic Stroke
dc.type.none.fl_str_mv Text
Journal contribution
info:eu-repo/semantics/publishedVersion
text
contribution to journal
description <div><p>Ischemic strokes are associated with significant morbidity and mortality, but currently there are no reliable prognostic or diagnostic blood biomarkers. MicroRNAs (miRNAs) regulate various molecular pathways and may be used as biomarkers. Using RNA-Seq, we conducted comprehensive circulating miRNA profiling in patients with ischemic stroke compared with healthy controls. Samples were collected within 24 h of clinical diagnosis. Stringent analysis criteria of discovery (46 cases and 95 controls) and validation (47 cases and 96 controls) cohorts led to the identification of 10 differentially regulated miRNAs, including 5 novel miRNAs, with potential diagnostic significance. Hsa-miR-451a was the most significantly upregulated miRNA (FC; 4.8, FDR; 3.78 × 10−85), while downregulated miRNAs included hsa-miR-574-5p and hsa-miR-142-3p, among others. Importantly, we computed a multivariate classifier based on the identified miRNA panel to differentiate between ischemic stroke patients and healthy controls, which showed remarkably high sensitivity (0.94) and specificity (0.99). The area under the ROC curve was 0.97 and it is superior to other current available biomarkers. Moreover, in samples collected one month following stroke, we found sustained upregulation of hsa-miR-451a and downregulation of another 5 miRNAs. Lastly, we report 3 miRNAs that were significantly associated with poor clinical outcomes of stroke, as defined by the modified Rankin scores. The clinical translation of the identified miRNA panel may be explored further.</p><p> </p></div><h2>Other Information</h2> <p> Published in: International Journal of Molecular Sciences<br> License: <a href="https://creativecommons.org/licenses/by/4.0/" target="_blank">https://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.3390/ijms23063387" target="_blank">https://dx.doi.org/10.3390/ijms23063387</a></p>
eu_rights_str_mv openAccess
id Manara2_6438f449abf6b96f4c6bfd3ff24c5f1a
identifier_str_mv 10.3390/ijms23063387
network_acronym_str Manara2
network_name_str Manara2
oai_identifier_str oai:figshare.com:article/25679838
publishDate 2022
repository.mail.fl_str_mv
repository.name.fl_str_mv
repository_id_str
rights_invalid_str_mv CC BY 4.0
spelling Identification of Novel Circulating miRNAs in Patients with Acute Ischemic StrokeEman K. Aldous (13914057)Salman M. Toor (8854751)Aijaz Parray (290256)Yasser Al-Sarraj (11721425)Ilhame Diboun (3522413)Essam M. Abdelalim (5768072)Abdelilah Arredouani (10914455)Omar El-Agnaf (2134222)Paul J. Thornalley (291723)Naveed Akhtar (4919398)Sajitha V. Pananchikkal (13914060)Ashfaq Shuaib (4919407)Nehad M. Alajez (7397276)Omar M. E. Albagha (11704871)Biomedical and clinical sciencesClinical sciencesNeurosciencesmicroRNAmiRNAischemic strokebiomarkers<div><p>Ischemic strokes are associated with significant morbidity and mortality, but currently there are no reliable prognostic or diagnostic blood biomarkers. MicroRNAs (miRNAs) regulate various molecular pathways and may be used as biomarkers. Using RNA-Seq, we conducted comprehensive circulating miRNA profiling in patients with ischemic stroke compared with healthy controls. Samples were collected within 24 h of clinical diagnosis. Stringent analysis criteria of discovery (46 cases and 95 controls) and validation (47 cases and 96 controls) cohorts led to the identification of 10 differentially regulated miRNAs, including 5 novel miRNAs, with potential diagnostic significance. Hsa-miR-451a was the most significantly upregulated miRNA (FC; 4.8, FDR; 3.78 × 10−85), while downregulated miRNAs included hsa-miR-574-5p and hsa-miR-142-3p, among others. Importantly, we computed a multivariate classifier based on the identified miRNA panel to differentiate between ischemic stroke patients and healthy controls, which showed remarkably high sensitivity (0.94) and specificity (0.99). The area under the ROC curve was 0.97 and it is superior to other current available biomarkers. Moreover, in samples collected one month following stroke, we found sustained upregulation of hsa-miR-451a and downregulation of another 5 miRNAs. Lastly, we report 3 miRNAs that were significantly associated with poor clinical outcomes of stroke, as defined by the modified Rankin scores. The clinical translation of the identified miRNA panel may be explored further.</p><p> </p></div><h2>Other Information</h2> <p> Published in: International Journal of Molecular Sciences<br> License: <a href="https://creativecommons.org/licenses/by/4.0/" target="_blank">https://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.3390/ijms23063387" target="_blank">https://dx.doi.org/10.3390/ijms23063387</a></p>2022-03-21T03:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.3390/ijms23063387https://figshare.com/articles/journal_contribution/Identification_of_Novel_Circulating_miRNAs_in_Patients_with_Acute_Ischemic_Stroke/25679838CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/256798382022-03-21T03:00:00Z
spellingShingle Identification of Novel Circulating miRNAs in Patients with Acute Ischemic Stroke
Eman K. Aldous (13914057)
Biomedical and clinical sciences
Clinical sciences
Neurosciences
microRNA
miRNA
ischemic stroke
biomarkers
status_str publishedVersion
title Identification of Novel Circulating miRNAs in Patients with Acute Ischemic Stroke
title_full Identification of Novel Circulating miRNAs in Patients with Acute Ischemic Stroke
title_fullStr Identification of Novel Circulating miRNAs in Patients with Acute Ischemic Stroke
title_full_unstemmed Identification of Novel Circulating miRNAs in Patients with Acute Ischemic Stroke
title_short Identification of Novel Circulating miRNAs in Patients with Acute Ischemic Stroke
title_sort Identification of Novel Circulating miRNAs in Patients with Acute Ischemic Stroke
topic Biomedical and clinical sciences
Clinical sciences
Neurosciences
microRNA
miRNA
ischemic stroke
biomarkers