Hyun Jae-Won, Payumo Rosah May Palermo, Chung Jieun, Kang You-Ri, Kim Su-Hyun, Kim Ho Jin, Han Ji-Youn, Park Sang-Yoon
Department of Neurology, Research Institute and Hospital of National Cancer Center, Goyang, Republic of Korea.
Center for Lung Cancer, Research Institute and Hospital of National Cancer Center, Goyang, Republic of Korea.
PLoS One. 2025 Jun 27;20(6):e0326654. doi: 10.1371/journal.pone.0326654. eCollection 2025.
Patients with cancer exhibit an increased risk of acute ischemic stroke (AIS), and neutrophil extracellular traposis (NETosis) has been proposed as a mechanism underlying cancer-associated hypercoagulability. However, studies validating these findings in independent cohorts are limited.
We sought to explore whether NETosis-associated markers (plasma DNA and nucleosomes) are increased in patients with active cancer and AIS, and whether these increases correlate with coagulopathy markers in cancer patients.
We analyzed NETosis-associated markers in cancer patients with and without AIS and healthy controls, and assessed the correlation between these markers and coagulopathy markers. Additionally, we compared the levels of Netosis-associated markers between cancer patients with conventional stroke mechanisms (CSM) and those with embolic stroke of undetermined source (ESUS).
Plasma DNA and nucleosome levels were significantly higher in cancer patients with AIS than in cancer controls and healthy controls (p < 0.001, respectively). Both markers correlated with D-dimer levels in cancer patients with AIS. In a sub-analysis, cancer patients with ESUS showed higher levels of NETosis-associated markers compared to those with CSM, whereas vascular risk factors were more frequently observed in cancer patients with CSM.
These findings suggest that NETosis may contribute to hypercoagulability in patients with active cancer and AIS, particularly in those with ESUS. These results provide additional evidence supporting the establishment of pathophysiology-based therapeutic approaches.
癌症患者发生急性缺血性卒中(AIS)的风险增加,中性粒细胞胞外陷阱形成(NETosis)被认为是癌症相关高凝状态的一种潜在机制。然而,在独立队列中验证这些发现的研究有限。
我们试图探讨在患有活动性癌症和AIS的患者中,NETosis相关标志物(血浆DNA和核小体)是否升高,以及这些升高是否与癌症患者的凝血病标志物相关。
我们分析了患有和未患有AIS的癌症患者以及健康对照者的NETosis相关标志物,并评估了这些标志物与凝血病标志物之间的相关性。此外,我们比较了具有传统卒中机制(CSM)的癌症患者和不明来源栓塞性卒中(ESUS)的癌症患者之间NETosis相关标志物的水平。
患有AIS的癌症患者的血浆DNA和核小体水平显著高于癌症对照者和健康对照者(分别为p < 0.001)。在患有AIS的癌症患者中,这两种标志物均与D-二聚体水平相关。在一项亚分析中,与患有CSM的患者相比,患有ESUS的癌症患者显示出更高水平的NETosis相关标志物,而在患有CSM的癌症患者中更频繁地观察到血管危险因素。
这些发现表明,NETosis可能导致患有活动性癌症和AIS的患者出现高凝状态,特别是在患有ESUS的患者中。这些结果提供了额外的证据,支持建立基于病理生理学的治疗方法。