Introduction 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 endometrial cancer.

Methods Circulating levels of three NET markers (histone-DNA complex, cell-free DNA, and neutrophil elastase) and prekallikrein were measured in 100 patients with endometrial cancer and 30 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 endometrial cancer showed significantly higher levels of the three NET markers and prekallikrein. Patients with advanced-stage endometrial cancer showed significantly higher levels of the cell-free DNA (P<0.001), compared with those with early-stage endometrial cancer. 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, 0.901). In multivariate analyses, neutrophil elastase was identified as an independent poor prognostic factor for overall survival and progression-free survival in patients with endometrial cancer.

Conclusion/Implications The levels of the three NET markers and prekallikrein might be novel diagnostic and prognostic markers for endometrial cancer.