Circulating Extracellular-Vesicle-Incorporated MicroRNAs as Potential Biomarkers for Ischemic Stroke in Patients With Cancer

Background and Purpose This study aimed to evaluate whether extracellular-vesicle-incorporated microRNAs (miRNAs) are potential biomarkers for cancer-related stroke. Methods This cohort study compared patients with active cancer who had embolic stroke of unknown sources (cancer-stroke group) with pa...

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Main Authors: Oh Young Bang, Eun Hee Kim, Mi Jeong Oh, Jaein Yoo, Gyun Sik Oh, Jong-Won Chung, Woo-Keun Seo, Gyeong-Moon Kim, Myung-Ju Ahn, Seong Wook Yang
Format: Article
Language:English
Published: Korean Stroke Society 2023-05-01
Series:Journal of Stroke
Subjects:
Online Access:http://www.j-stroke.org/upload/pdf/jos-2022-02327.pdf
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author Oh Young Bang
Eun Hee Kim
Mi Jeong Oh
Jaein Yoo
Gyun Sik Oh
Jong-Won Chung
Woo-Keun Seo
Gyeong-Moon Kim
Myung-Ju Ahn
Seong Wook Yang
author_facet Oh Young Bang
Eun Hee Kim
Mi Jeong Oh
Jaein Yoo
Gyun Sik Oh
Jong-Won Chung
Woo-Keun Seo
Gyeong-Moon Kim
Myung-Ju Ahn
Seong Wook Yang
author_sort Oh Young Bang
collection DOAJ
description Background and Purpose This study aimed to evaluate whether extracellular-vesicle-incorporated microRNAs (miRNAs) are potential biomarkers for cancer-related stroke. Methods This cohort study compared patients with active cancer who had embolic stroke of unknown sources (cancer-stroke group) with patients with only cancer, patients with only stroke, and healthy individuals (control groups). The expression profiles of miRNAs encapsulated in plasma exosomes and microvesicles were evaluated using microarray and validated using quantitative real-time polymerase chain reaction. The XENO-QTM miRNA assay technology was used to determine the absolute copy numbers of individual miRNAs in an external validation cohort. Results This study recruited 220 patients, of which 45 had cancer-stroke, 76 were healthy controls, 39 were cancer controls, and 60 were stroke controls. Three miRNAs (miR-205-5p, miR-645, and miR-646) were specifically incorporated into microvesicles in patients with cancer-related stroke, cancer controls, and stroke controls. The area under the receiver operating characteristic curves of these three miRNAs were 0.7692–0.8510 for the differentiation of patients with cancer-stroke from cancer-controls and 0.8077–0.8846 for the differentiation of patients with cancer-stroke from stroke controls. The levels of several miRNAs were elevated in the plasma exosomes of patients with cancer, but were lower than those in plasma microvesicles. An in vivo study showed that systemic injection of miR-205-5p promoted the development of arterial thrombosis and elevation of D-dimer levels Conclusion Stroke due to cancer-related coagulopathy was associated with deregulated expression of miRNAs, particularly microvesicle-incorporated miR-205-5p, miR-645, and miR-646. Further prospective studies of extracellular-vesicle-incorporated miRNAs are required to confirm the diagnostic role of miRNAs in patients with stroke and to screen the roles of miRNAs in patients with cancer.
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spelling doaj.art-5d7fb4a72a3e4b26a91b945914b65de42023-10-23T00:17:46ZengKorean Stroke SocietyJournal of Stroke2287-63912287-64052023-05-0125225126510.5853/jos.2022.02327481Circulating Extracellular-Vesicle-Incorporated MicroRNAs as Potential Biomarkers for Ischemic Stroke in Patients With CancerOh Young Bang0Eun Hee Kim1Mi Jeong Oh2Jaein Yoo3Gyun Sik Oh4Jong-Won Chung5Woo-Keun Seo6Gyeong-Moon Kim7Myung-Ju Ahn8Seong Wook Yang9 Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea S&E bio Co., Ltd., Seoul, Korea Translational and Stem Cell Research Laboratory on Stroke, Samsung Medical Center, Seoul, Korea Translational and Stem Cell Research Laboratory on Stroke, Samsung Medical Center, Seoul, Korea S&E bio Co., Ltd., Seoul, Korea Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea Department of Hemato-Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul, KoreaBackground and Purpose This study aimed to evaluate whether extracellular-vesicle-incorporated microRNAs (miRNAs) are potential biomarkers for cancer-related stroke. Methods This cohort study compared patients with active cancer who had embolic stroke of unknown sources (cancer-stroke group) with patients with only cancer, patients with only stroke, and healthy individuals (control groups). The expression profiles of miRNAs encapsulated in plasma exosomes and microvesicles were evaluated using microarray and validated using quantitative real-time polymerase chain reaction. The XENO-QTM miRNA assay technology was used to determine the absolute copy numbers of individual miRNAs in an external validation cohort. Results This study recruited 220 patients, of which 45 had cancer-stroke, 76 were healthy controls, 39 were cancer controls, and 60 were stroke controls. Three miRNAs (miR-205-5p, miR-645, and miR-646) were specifically incorporated into microvesicles in patients with cancer-related stroke, cancer controls, and stroke controls. The area under the receiver operating characteristic curves of these three miRNAs were 0.7692–0.8510 for the differentiation of patients with cancer-stroke from cancer-controls and 0.8077–0.8846 for the differentiation of patients with cancer-stroke from stroke controls. The levels of several miRNAs were elevated in the plasma exosomes of patients with cancer, but were lower than those in plasma microvesicles. An in vivo study showed that systemic injection of miR-205-5p promoted the development of arterial thrombosis and elevation of D-dimer levels Conclusion Stroke due to cancer-related coagulopathy was associated with deregulated expression of miRNAs, particularly microvesicle-incorporated miR-205-5p, miR-645, and miR-646. Further prospective studies of extracellular-vesicle-incorporated miRNAs are required to confirm the diagnostic role of miRNAs in patients with stroke and to screen the roles of miRNAs in patients with cancer.http://www.j-stroke.org/upload/pdf/jos-2022-02327.pdfcancerstrokecoagulopathybiomarkerextracellular vesiclemicrorna
spellingShingle Oh Young Bang
Eun Hee Kim
Mi Jeong Oh
Jaein Yoo
Gyun Sik Oh
Jong-Won Chung
Woo-Keun Seo
Gyeong-Moon Kim
Myung-Ju Ahn
Seong Wook Yang
Circulating Extracellular-Vesicle-Incorporated MicroRNAs as Potential Biomarkers for Ischemic Stroke in Patients With Cancer
Journal of Stroke
cancer
stroke
coagulopathy
biomarker
extracellular vesicle
microrna
title Circulating Extracellular-Vesicle-Incorporated MicroRNAs as Potential Biomarkers for Ischemic Stroke in Patients With Cancer
title_full Circulating Extracellular-Vesicle-Incorporated MicroRNAs as Potential Biomarkers for Ischemic Stroke in Patients With Cancer
title_fullStr Circulating Extracellular-Vesicle-Incorporated MicroRNAs as Potential Biomarkers for Ischemic Stroke in Patients With Cancer
title_full_unstemmed Circulating Extracellular-Vesicle-Incorporated MicroRNAs as Potential Biomarkers for Ischemic Stroke in Patients With Cancer
title_short Circulating Extracellular-Vesicle-Incorporated MicroRNAs as Potential Biomarkers for Ischemic Stroke in Patients With Cancer
title_sort circulating extracellular vesicle incorporated micrornas as potential biomarkers for ischemic stroke in patients with cancer
topic cancer
stroke
coagulopathy
biomarker
extracellular vesicle
microrna
url http://www.j-stroke.org/upload/pdf/jos-2022-02327.pdf
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