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.

中文翻译：

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循环细胞外囊泡掺入 MicroRNA 作为癌症患者缺血性中风的潜在生物标志物。

背景和目的 本研究旨在评估细胞外囊泡掺入的 microRNA (miRNA) 是否是癌症相关中风的潜在生物标志物。方法 本队列研究比较了患有不明原因栓塞性卒中的活动性癌症患者（癌症卒中组）与仅患有癌症的患者、仅患有卒中的患者和健康个体（对照组）。使用微阵列评估封装在血浆外泌体和微泡中的 miRNA 的表达谱，并使用定量实时聚合酶链反应进行验证。XENO-QTM miRNA 检测技术用于确定外部验证队列中单个 miRNA 的绝对拷贝数。结果 本研究招募了 220 名患者，其中 45 名患有癌症卒中，76 名健康对照者，39 名癌症对照者，60 例是中风对照。三种 miRNA（miR-205-5p、miR-645 和 miR-646）被特异性整合到癌症相关中风患者、癌症对照者和中风对照者的微泡中。这三种 miRNA 的受试者工作特征曲线下面积分别为 0.7692-0.8510 和 0.8077-0.8846，用于区分癌症卒中患者和癌症对照患者。几种 miRNA 的水平在癌症患者的血浆外泌体中升高，但低于血浆微泡中的水平。一项体内研究表明，全身注射 miR-205-5p 促进了动脉血栓形成的发展和 D-二聚体水平的升高。结论 癌症相关凝血病引起的中风与 miRNA 表达失调相关，尤其是微泡掺入的 miR-205-5p、miR-645 和 miR-646。需要对细胞外囊泡掺入的 miRNA 进行进一步的前瞻性研究，以确认 miRNA 在中风患者中的诊断作用，并筛选 miRNA 在癌症患者中的作用。