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Abstract：
OBJECTIVE: Neutrophils produce neutrophil extracellular traps (NETs) by releasing nuclear contents into the extracellular environment. NETs are associated with systemic inflammation and cancer development and progression. We aimed to investigate whether NET markers are associated with the prognosis of endometrial cancer.
METHODS: Circulating levels of three NET markers (histone-DNA complex, cell-free double-stranded DNA (dsDNA), and neutrophil elastase) were measured in 98 patients with endometrial cancer who underwent surgery as primary treatment between January 2015 and June 2018 and 45 healthy women. Area under the receiver operating characteristic curve (AUC) analyses were conducted to investigate the diagnostic and prognostic utility of the markers for endometrial cancer.
RESULTS: Patients with endometrial cancer showed significantly higher levels of the three NET markers than those in healthy controls. In discriminating endometrial cancer patients from healthy controls, the three NET markers showed AUC values in the following order: cell-free dsDNA (0.832; 95 % CI, 0.760-0.889), histone-DNA complex (0.740; 95 % CI, 0.660-0.809), and neutrophil elastase (0.689; 95 % CI, 0.607-0.764), comparable to those of CA-125 (0.741; 95 % CI, 0.659-0.813). Multivariate analysis adjusting for FIGO stage, histology, and lymphovascular space invasion, and lymph node involvement revealed that cell-free dsDNA level (cutoff: 95.2 ng/mL) was an independent prognostic marker for poor progression-free (adjusted HR, 2.75; 95 % CI, 1.096.92; P = 0.032) and overall survival (adjusted HR, 11.51; 95 % CI, 2.0664.22; P = 0.005) for patients with endometrial cancer.
CONCLUSIONS: High levels of circulating NET markers were observed in patients with endometrial cancer. Cell-free dsDNA levels may play a role as prognostic markers for endometrial cancer.
METHODS: Circulating levels of three NET markers (histone-DNA complex, cell-free double-stranded DNA (dsDNA), and neutrophil elastase) were measured in 98 patients with endometrial cancer who underwent surgery as primary treatment between January 2015 and June 2018 and 45 healthy women. Area under the receiver operating characteristic curve (AUC) analyses were conducted to investigate the diagnostic and prognostic utility of the markers for endometrial cancer.
RESULTS: Patients with endometrial cancer showed significantly higher levels of the three NET markers than those in healthy controls. In discriminating endometrial cancer patients from healthy controls, the three NET markers showed AUC values in the following order: cell-free dsDNA (0.832; 95 % CI, 0.760-0.889), histone-DNA complex (0.740; 95 % CI, 0.660-0.809), and neutrophil elastase (0.689; 95 % CI, 0.607-0.764), comparable to those of CA-125 (0.741; 95 % CI, 0.659-0.813). Multivariate analysis adjusting for FIGO stage, histology, and lymphovascular space invasion, and lymph node involvement revealed that cell-free dsDNA level (cutoff: 95.2 ng/mL) was an independent prognostic marker for poor progression-free (adjusted HR, 2.75; 95 % CI, 1.096.92; P = 0.032) and overall survival (adjusted HR, 11.51; 95 % CI, 2.0664.22; P = 0.005) for patients with endometrial cancer.
CONCLUSIONS: High levels of circulating NET markers were observed in patients with endometrial cancer. Cell-free dsDNA levels may play a role as prognostic markers for endometrial cancer.
摘要：
目的：中性粒细胞通过将核内容物释放到细胞外环境中来产生中性粒细胞胞外陷阱（NETs）。NET与全身性炎症和癌症的发展和进展有关。我们旨在研究NET标记物是否与子宫内膜癌的预后相关。
方法：三个NET标记的循环水平（组蛋白-DNA复合物，无细胞双链DNA(dsDNA),和中性粒细胞弹性蛋白酶）在2015年1月至2018年6月期间接受手术作为主要治疗的98例子宫内膜癌患者和45例健康女性中进行了测量。进行受试者工作特征曲线下面积（AUC）分析以研究子宫内膜癌标志物的诊断和预后效用。
结果：子宫内膜癌患者的三种NET标志物水平明显高于健康对照组。在区分子宫内膜癌患者与健康对照时，三个NET标记显示AUC值按以下顺序：无细胞dsDNA（0.832；95％CI，0.760-0.889），组蛋白-DNA复合物（0.740；95%CI，0.660-0.809），和中性粒细胞弹性蛋白酶（0.689；95%CI，0.607-0.764），与CA-125相当（0.741；95%CI，0.659-0.813）。针对FIGO阶段进行多变量分析调整，组织学,和淋巴管间隙侵入，和淋巴结受累显示，无细胞dsDNA水平（截止：95.2ng/mL）是无进展不良的独立预后标志物（调整后的HR，2.75；95%CI，1.096.92；P=0.032）和总生存期（调整后的HR，11.51；子宫内膜癌患者的95%CI，2.0664.22；P=0.005）。
结论：在子宫内膜癌患者中观察到高水平的循环NET标志物。无细胞dsDNA水平可能作为子宫内膜癌的预后标志物发挥作用。
方法：三个NET标记的循环水平（组蛋白-DNA复合物，无细胞双链DNA(dsDNA),和中性粒细胞弹性蛋白酶）在2015年1月至2018年6月期间接受手术作为主要治疗的98例子宫内膜癌患者和45例健康女性中进行了测量。进行受试者工作特征曲线下面积（AUC）分析以研究子宫内膜癌标志物的诊断和预后效用。
结果：子宫内膜癌患者的三种NET标志物水平明显高于健康对照组。在区分子宫内膜癌患者与健康对照时，三个NET标记显示AUC值按以下顺序：无细胞dsDNA（0.832；95％CI，0.760-0.889），组蛋白-DNA复合物（0.740；95%CI，0.660-0.809），和中性粒细胞弹性蛋白酶（0.689；95%CI，0.607-0.764），与CA-125相当（0.741；95%CI，0.659-0.813）。针对FIGO阶段进行多变量分析调整，组织学,和淋巴管间隙侵入，和淋巴结受累显示，无细胞dsDNA水平（截止：95.2ng/mL）是无进展不良的独立预后标志物（调整后的HR，2.75；95%CI，1.096.92；P=0.032）和总生存期（调整后的HR，11.51；子宫内膜癌患者的95%CI，2.0664.22；P=0.005）。
结论：在子宫内膜癌患者中观察到高水平的循环NET标志物。无细胞dsDNA水平可能作为子宫内膜癌的预后标志物发挥作用。
