Prognostic value of serum NETosis indices in advanced ovarian cancer

Introduction. Increased formation of neutrophil extracellular traps (NETosis) by activated neutrophils causes the development of a number of pathological processes, i.e., NETopathy. The role of neutrophil traps in the progression of malignant tumors of various localizations has been shown. NETosis indicators may have prognostic significance in ovarian cancer. Aim. Evaluation of the prognostic significance of serum NETosis indices in advanced ovarian cancer. Materials and Methods . In the circulating blood of patients with stage III and IV malignant neoplasms and benign ovarian tumors, the neutrophil extracellular trap parameters were assessed, as well as the level of vascular endothelial growth factor (VEGF) – A, interleukin (IL) – 1β, neutrophil elastase (NE), and neutrophil-lymphocyte ratio (NLR) by ELISA. For statistical processing, the Statistica 13.0 and Jamovi 2.4.14 software programs were used. Results and Discussion. In patients with advanced ovarian cancer, the levels of IL-1β, VEGF-A, NE, and NLR significantly increase, in comparison with both the control and the values in patients with benign ovarian tumors. In multivariate Cox analysis, progression-free time (PFT) depended on the number of neutrophil extracellular traps (HR 0.61, 95% CI 0.46-0.81, p=0.001), NLR (HR 0.82, 95% CI 0.72-0.93, p=0.002), and VEGF level (HR 1.29, 95% CI 1.09-1.53, p=0.034) in blood plasma in women with ascites (HR 2.81, 95% CI 1.33-5.94, p=0.007) over 69 years old (HR 3.57, 95% CI 1.40-9.10, p=0.008). Ovarian cancer metastasis risk increases with an increase in VEGF and the number of neutrophil traps in the blood (R2 = 0.589, χ² = 47.3, p = 0.001) (specificity = 0.929, sensitivity = 0.867). When the number of neutrophil traps increases (cut points=3), the median PFT is 9.3 [6.4 – 34.5, 95% CI] months; when the level of VEGF-A in the blood increases (cut point=849), the median PFT is 7.6 [3.6 – 27.7, 95% CI] months. Conclusions . In advanced ovarian cancer, the following NETosis indices change significantly in the blood serum: NE, VEGF-A, and NLR, which can be used to assess the time without progression, differential diagnosis of stages III and IV ovarian cancer, and risk of relapse.