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Stroke. 2019 Aug 9:STROKEAHA119026373. doi: 10.1161/STROKEAHA.119.026373. [Epub ahead of print]

Circulating DNAs, a Marker of Neutrophil Extracellular Traposis and Cancer-Related Stroke.

Author information

1
From the Department of Neurology, Samsung Medical Center, School of Medicine, Sungkyunkwan University, Seoul, South Korea (O.Y.B., J.-W.C., W.-K.S., G.-M.K.).
2
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.).
3
Department of Hemato-oncology, Samsung Medical Center, School of Medicine, Sungkyunkwan University, Seoul, South Korea- (M.-J.A.).

Abstract

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 (P<0.05). These levels were correlated with the D-dimer levels (P<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.

KEYWORDS:

biomarkers; cancer; cerebral stroke; extracellular traps; nucleosomes; plasma; thrombosis

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