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

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.