دورية أكاديمية
Decoding Molecular Mechanisms Underlying Outcomes After Ischemic Stroke Thrombectomy by RNA Sequencing of Retrieved Clots.
| العنوان: | Decoding Molecular Mechanisms Underlying Outcomes After Ischemic Stroke Thrombectomy by RNA Sequencing of Retrieved Clots. |
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| المؤلفون: | Santo BA; Canon Stroke and Vascular Research Center, University at Buffalo, 875 Ellicott Street, Buffalo, NY, 14203, USA.; Department of Pathology and Anatomical Sciences, University at Buffalo, Buffalo, NY, USA.; Department of Neurosurgery, University at Buffalo, Buffalo, NY, USA., Poppenberg KE; Canon Stroke and Vascular Research Center, University at Buffalo, 875 Ellicott Street, Buffalo, NY, 14203, USA., Ciecierska SS; Canon Stroke and Vascular Research Center, University at Buffalo, 875 Ellicott Street, Buffalo, NY, 14203, USA., Lim J; Canon Stroke and Vascular Research Center, University at Buffalo, 875 Ellicott Street, Buffalo, NY, 14203, USA.; Department of Neurosurgery, University at Buffalo, Buffalo, NY, USA., Baig AA; Canon Stroke and Vascular Research Center, University at Buffalo, 875 Ellicott Street, Buffalo, NY, 14203, USA.; Department of Neurosurgery, University at Buffalo, Buffalo, NY, USA., Jaikumar V; Canon Stroke and Vascular Research Center, University at Buffalo, 875 Ellicott Street, Buffalo, NY, 14203, USA.; Department of Neurosurgery, University at Buffalo, Buffalo, NY, USA., Raygor KP; Canon Stroke and Vascular Research Center, University at Buffalo, 875 Ellicott Street, Buffalo, NY, 14203, USA.; Department of Neurosurgery, University at Buffalo, Buffalo, NY, USA., Patel TR; Canon Stroke and Vascular Research Center, University at Buffalo, 875 Ellicott Street, Buffalo, NY, 14203, USA.; Department of Neurosurgery, University at Buffalo, Buffalo, NY, USA., Shah M; Canon Stroke and Vascular Research Center, University at Buffalo, 875 Ellicott Street, Buffalo, NY, 14203, USA., Levy EI; Canon Stroke and Vascular Research Center, University at Buffalo, 875 Ellicott Street, Buffalo, NY, 14203, USA.; Department of Neurosurgery, University at Buffalo, Buffalo, NY, USA., Siddiqui AH; Canon Stroke and Vascular Research Center, University at Buffalo, 875 Ellicott Street, Buffalo, NY, 14203, USA.; Department of Neurosurgery, University at Buffalo, Buffalo, NY, USA., Tutino VM; Canon Stroke and Vascular Research Center, University at Buffalo, 875 Ellicott Street, Buffalo, NY, 14203, USA. vincentt@buffalo.edu.; Department of Pathology and Anatomical Sciences, University at Buffalo, Buffalo, NY, USA. vincentt@buffalo.edu.; Department of Neurosurgery, University at Buffalo, Buffalo, NY, USA. vincentt@buffalo.edu. |
| المصدر: | Molecular diagnosis & therapy [Mol Diagn Ther] 2024 Jul; Vol. 28 (4), pp. 469-477. Date of Electronic Publication: 2024 May 20. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Adis, Springer International Country of Publication: New Zealand NLM ID: 101264260 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1179-2000 (Electronic) Linking ISSN: 11771062 NLM ISO Abbreviation: Mol Diagn Ther Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Auckland : Adis, Springer International Original Publication: Auckland, N.Z. : Adis International, c2006- |
| مواضيع طبية MeSH: | Thrombectomy* , Ischemic Stroke*/genetics , Ischemic Stroke*/metabolism , Ischemic Stroke*/surgery , Transcriptome* , Gene Expression Profiling*, Humans ; Male ; Female ; Aged ; Middle Aged ; Computational Biology/methods ; Treatment Outcome ; Sequence Analysis, RNA ; Gene Ontology ; Thrombosis/genetics ; Thrombosis/etiology ; Gene Regulatory Networks |
| مستخلص: | Background: Transcriptomic profiling has emerged as a powerful tool for exploring the molecular landscape of ischemic stroke clots and providing insights into the pathophysiological mechanisms underlying stroke progression and recovery. In this study, we aimed to investigate the relationship between stroke clot transcriptomes and stroke thrombectomy outcome, as measured by early neurological improvement (ENI) 30 (i.e., a 30% reduction in NIHSS at 24 h post-thrombectomy). Hypothesis: We hypothesized that there exist distinct clot gene expression patterns between good and poor neurological outcomes. Methods: Transcriptomic analysis of 32 stroke clots retrieved by mechanical thrombectomy was conducted. Transcriptome data of these clots were analyzed to identify differentially expressed genes (DEGs), defined as those with a log(fold-change) ≥ 1.5 and q < 0.05 between samples with good and poor early neurological outcomes. Gene ontology and bioinformatics analyses were performed on genes with p < 0.01 to identify enriched biological processes and Ingenuity Pathway Analysis canonical pathways. Moreover, AUC analysis assessed the predictive power of DEGs for 90-day function outcome (mRS ≤ 2) and cellular composition of clot was predicted using CIBERSORT. We also assessed whether differential enrichment of immune cell types could indicate patient survival. Results: A total of 41 DEGs were identified. Bioinformatics showed that enriched biological processes and pathways emphasized the chronic immune response and matrix metalloproteinase inhibition. Moreover, 25 of the DEGs were found to be significant predictors of 90-day mRS. These genes were indicative of monocytes enrichment and neutrophil depletion in patients with poorer outcomes. Conclusion: Our study revealed a distinct gene expression pattern and dysregulated biological pathways associated with ENI. This expression pattern was also predictive of long-term outcome, suggesting a biological link between those ENIs and 90-day mRS. (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.) |
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| معلومات مُعتمدة: | UL1TR001412 United States GF NIH HHS |
| تواريخ الأحداث: | Date Created: 20240520 Date Completed: 20240627 Latest Revision: 20240627 |
| رمز التحديث: | 20240627 |
| DOI: | 10.1007/s40291-024-00716-y |
| PMID: | 38769267 |
| قاعدة البيانات: | MEDLINE |
Find this article in full text from Springer Verlag. 
Full Text Finder | تدمد: | 1179-2000 |
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| DOI: | 10.1007/s40291-024-00716-y |