Circulating markers of neutrophil extracellular traps (NETs) in patients with ovarian tumors

Abstract Background Inflammation is a hallmark of cancer, and emerging light is being shed on the neutrophil release of nuclear chromatin, referred to as neutrophil extracellular traps (NETs) in cancer and cancer associated thrombosis. The NET-specific marker citrullinated histone H3 (H3Cit) has been found to be elevated in plasma from patients with malignancies, suggesting the potential of NET markers, such as H3Cit, as novel cancer biomarkers. Objective To determine the levels of plasma H3Cit in blood in women with adnexal masses. Subjects and Method s: Peripheral blood samples were obtained preoperatively from 199 patients admitted for primary surgery of adnexal masses 2015–2017. Patients were grouped according to tumor type and stage of cancer. Plasma levels of H3Cit-DNA, cell free DNA (cfDNA) and the clinically implemented tumor marker cancer antigen 125 (CA125) were determined with ELISA. Results Plasma levels of H3Cit-DNA and cfDNA were not elevated in women with borderline or malignant ovarian tumors compared with women with benign tumors. Increased plasma levels of CA125 were detected in borderline and ovarian cancer stage I and stage II-IV compared with benign ovarian tumor patients (ptrend<0.001). In Cox regression analysis high levels of Ca 125 dichotomized at 326 IU/ml (median) showed worse overall survival hazard ratio 1.9 (95 % C.I. 1.03–3.36; p = 0.038). No differences were found in the survival analyses in malignant ovarian tumors analyzing the cfDNA and H3Cit-DNA levels. Conclusion This study did not find any association nor prognostic association between the plasma levels of the NET marker H3Cit and ovarian cancer patients.