Identification of Novel Circulating miRNAs in Patients with Acute Ischemic Stroke.

Autor: Aldous EK; College of Health and Life Sciences (CHLS), Hamad Bin Khalifa University (HBKU), Qatar Foundation (QF), Doha P.O. Box 34110, Qatar.; Diabetes Research Center, Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Qatar Foundation (QF), Doha P.O. Box 34110, Qatar., Toor SM; College of Health and Life Sciences (CHLS), Hamad Bin Khalifa University (HBKU), Qatar Foundation (QF), Doha P.O. Box 34110, Qatar., Parray A; The Neuroscience Institute, Academic Health System, Hamad Medical Corporation (HMC), Doha P.O. Box 3050, Qatar., Al-Sarraj Y; College of Health and Life Sciences (CHLS), Hamad Bin Khalifa University (HBKU), Qatar Foundation (QF), Doha P.O. Box 34110, Qatar.; Diabetes Research Center, Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Qatar Foundation (QF), Doha P.O. Box 34110, Qatar., Diboun I; College of Health and Life Sciences (CHLS), Hamad Bin Khalifa University (HBKU), Qatar Foundation (QF), Doha P.O. Box 34110, Qatar., Abdelalim EM; College of Health and Life Sciences (CHLS), Hamad Bin Khalifa University (HBKU), Qatar Foundation (QF), Doha P.O. Box 34110, Qatar.; Diabetes Research Center, Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Qatar Foundation (QF), Doha P.O. Box 34110, Qatar., Arredouani A; Diabetes Research Center, Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Qatar Foundation (QF), Doha P.O. Box 34110, Qatar., El-Agnaf O; Neurological Disorders Research Center, Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Qatar Foundation (QF), Doha P.O. Box 34110, Qatar., Thornalley PJ; Diabetes Research Center, Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Qatar Foundation (QF), Doha P.O. Box 34110, Qatar., Akhtar N; The Neuroscience Institute, Academic Health System, Hamad Medical Corporation (HMC), Doha P.O. Box 3050, Qatar., Pananchikkal SV; The Neuroscience Institute, Academic Health System, Hamad Medical Corporation (HMC), Doha P.O. Box 3050, Qatar., Shuaib A; Division of Neurology, Department of Medicine, University of Alberta, Edmonton, AB T6G 2R3, Canada.; Department of Neurology, Hamad Medical Corporation (HMC), Doha P.O. Box 3050, Qatar., Alajez NM; College of Health and Life Sciences (CHLS), Hamad Bin Khalifa University (HBKU), Qatar Foundation (QF), Doha P.O. Box 34110, Qatar.; Translational Cancer and Immunity Center, Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Qatar Foundation (QF), Doha P.O. Box 34110, Qatar., Albagha OME; College of Health and Life Sciences (CHLS), Hamad Bin Khalifa University (HBKU), Qatar Foundation (QF), Doha P.O. Box 34110, Qatar.; Diabetes Research Center, Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Qatar Foundation (QF), Doha P.O. Box 34110, Qatar.; Rheumatology and Bone Disease Unit, Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh EH4 2XU, UK.
Jazyk: angličtina
Zdroj: International journal of molecular sciences [Int J Mol Sci] 2022 Mar 21; Vol. 23 (6). Date of Electronic Publication: 2022 Mar 21.
DOI: 10.3390/ijms23063387
Abstrakt: 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.
Databáze: MEDLINE
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