Diagnostic and prognostic role of circulating neutrophil extracellular trap markers and prekallikrein in patients with high-grade serous ovarian cancer

OBJECTIVE: Tumor-promoting inflammation is among the hallmarks of cancer. Prekallikrein is among the acute-phase reactants in the inflammatory response; moreover, neutrophils release nuclear contents into the extracellular space to create neutrophil extracellular traps (NET). We aimed to investigate the diagnostic and prognostic utilities of circulating plasma NET markers and prekallikrein for high-grade serous ovarian cancer (HGSOC). METHODS: Circulating levels of three NET markers (histone-DNA complex, cell-free DNA, and neutrophil elastase) and prekallikrein were measured in 75 patients with HGSOC and 23 healthy controls. We used an area under the receiver operating characteristic curve (AUC) analysis to investigate their diagnostic and prognostic utilities for HGSOC. RESULTS: Compared with healthy controls, patients with HGSOC showed significantly higher levels of the three NET markers and prekallikrein. Patients with advanced-stage HGSOC showed significantly higher levels of the cell-free DNA (87.4 vs. 79.5 ng/ml; P = 0.013), compared with those with early-stage HGSOC. Further, the levels of histone-DNA complex, neutrophil elastase, and prekallikrein did not significantly differ according to the cancer stage. All markers showed significant diagnostic utility. Notably, a logistic regression-based model that comprised all four markers showed the strongest diagnostic power (AUC, 0.966; 95% confidence interval [CI], 0.933−1.000). Specifically, neutrophil elastase was identified as an independent poor prognostic factor for overall survival (adjusted hazard ratio [aHR], 10.17; 95% CI, 1.09−94.97; P = 0.042) and progression-free survival (aHR, 14.47; 95% CI, 1.52−137.35; P = 0.020) in patients with HGSOC. CONCLUSIONS: The levels of the three NET markers and prekallikrein might be novel diagnostic and prognostic markers for HGSOC.