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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2022
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| _version_ | 1864513518516043776 |
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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 |