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

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

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

Abstract

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-Q™ 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.

Original languageEnglish
Pages (from-to)251-265
Number of pages15
JournalJournal of Stroke
Volume25
Issue number2
DOIs
Publication statusPublished - 2023 May

Bibliographical note

Publisher Copyright:
© 2023 Korean Stroke Society.

All Science Journal Classification (ASJC) codes

  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

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