From the Department of Neurology (O.Y.B., J.-W.C., W.-K.S., G.-M.K.), Samsung Medical Center, School of Medicine, Sungkyunkwan University, Seoul, South Korea.
Translational and Stem Cell Research Laboratory on Stroke, Samsung Medical Center, Seoul, South Korea (O.Y.B., J.-W.C., Y.H.C., M.J.O.).
Stroke. 2019 Oct;50(10):2944-2947. doi: 10.1161/STROKEAHA.119.026373. Epub 2019 Aug 9.
Background and Purpose- The role of circulating neutrophil extracellular traps (NETs) in cancer-related stroke is unknown. Methods- We conducted a prospective cohort study to test whether NETs are increased in cancer-related stroke and whether elevated NETs levels are associated with coagulopathy, assessed using D-dimer levels (≥2 μg/mL). Plasma DNA and nucleosome were assessed as NET-specific biomarkers. Results- In total, 138 patients were recruited; 38 patients had cancer-related stroke (active cancer and acute cryptogenic embolic stroke), 33 patients were healthy-controls, 27 patients were cancer-controls (active cancer but no stroke), and 40 patients were stroke-controls (acute ischemic stroke but no cancer). Plasma DNA and nucleosome levels were significantly elevated in cancer-related stroke patients than in healthy-controls (<0.05). These levels were correlated with the D-dimer levels (<0.01). In multiple regression analyses, increased plasma DNA levels were associated with cancer-related stroke (odds ratio=11.65 for highest quartile; 95% CI, 3.199-42.46) and D-dimer levels of ≥2 μg/mL (odds ratio=19.09 for highest quartile; 95% CI, 4.143-87.95) after adjusting for possible confounders. Conclusions- Increased circulating DNA levels were associated with cancer-related stroke, suggesting that NETosis is one of the molecular mechanisms of cancer-related stroke. Further long-term follow-up studies in large cohorts are needed to confirm the role of NET-specific biomarkers.
循环中性粒细胞胞外诱捕网（NETs）在癌症相关卒中中的作用尚不清楚。方法：我们进行了一项前瞻性队列研究，以测试 NETs 是否在癌症相关卒中患者中增加，以及 NETs 水平升高是否与凝血障碍相关，评估指标为 D-二聚体水平（≥2μg/mL）。血浆 DNA 和核小体被评估为 NET 特异性生物标志物。结果：共招募了 138 例患者；38 例为癌症相关卒中（活动性癌症和急性隐源性栓塞性卒中），33 例为健康对照，27 例为癌症对照（活动性癌症但无卒中），40 例为卒中对照（急性缺血性卒中但无癌症）。癌症相关卒中患者的血浆 DNA 和核小体水平明显高于健康对照组（<0.05）。这些水平与 D-二聚体水平相关（<0.01）。在多变量回归分析中，增加的血浆 DNA 水平与癌症相关卒中相关（最高四分位数的优势比为 11.65；95%CI，3.199-42.46）和 D-二聚体水平≥2μg/mL（最高四分位数的优势比为 19.09；95%CI，4.143-87.95），在调整了可能的混杂因素后。结论：循环 DNA 水平升高与癌症相关卒中相关，提示 NETosis 是癌症相关卒中的分子机制之一。需要进一步在大型队列中进行长期随访研究，以确认 NET 特异性生物标志物的作用。
