When cells die, nucleosomes composed of DNA and histone proteins enter the extracellular space and end eventually in the circulation. In plasma, they might serve as a nonspecific marker of cell death, potentially useful for noninvasive monitoring of tumor dynamics. The aim of this study was to analyze circulating nucleosomes in relation to patient/tumor characteristics and prognosis in primary breast cancer. This study included 92 patients with breast cancer treated with surgery for whom plasma isolated was available in the biobank. Plasma nucleosomes were detected in samples taken in the morning on the day of surgery using Cell Death Detection ELISA kit with anti-histone and anti-DNA antibodies. Circulating nucleosomes were positively associated with the systemic inflammatory index (SII), but not with other patient/tumor characteristics. Patients with high SII in comparison to low SII had higher circulating nucleosomes (by 59%, p = 0.02). Nucleosomes correlated with plasma plasminogen activator inhibitor-1, IL-15, IL-16, IL-18, and hepatocyte growth factor. Patients with lower nucleosomes had significantly better disease-free survival (HR = 0.46, p = 0.05). In a multivariate analysis, nucleosomes, hormone receptor status, HER2 status, lymph node involvement, and tumor grade were independent predictors of disease-free survival. Our data suggest that plasma nucleosomes in primary breast cancer are associated with systemic inflammation and might have a prognostic value. The underlying mechanisms require further studies.
Keywords: circulating nucleosomes; circulating tumor cells; cytokines; plasminogen activator inhibitor-1; primary breast cancer.