血清sCD73、S100A8/A9水平与晚期子宫内膜癌患者临床病理特征及PD-1/PD-L1抑制剂治疗预后的关联性分析

Analysis on the correlation of serum sCD73 and S100A8/A9 levels with clinicopathological features and therapeutic prognosis of PD-1/PD-L1 inhibitors in patients with advanced endometrial cancer

目的 分析血清可溶性CD73(sCD73)、S100钙结合蛋白A8/A9(S100A8/A9)与晚期子宫内膜癌患者临床病理特征及程序性死亡受体-1(PD-1)/程序性死亡配体1(PD-L1)抑制剂治疗预后的关联性。方法 招募2020年3月至2021年2月于齐齐哈尔市第一医院接受PD-1/PD-L1抑制剂治疗的晚期子宫内膜癌患者142例,入院后于晨间采集空腹肘部静脉血5 mL,取血清,采用酶联免疫吸附法测定患者血清sCD73、S100A8/A9水平。在随访期间,有58例患者死亡(死亡组),84例存活(存活组)。采用受试者工作特征(ROC)曲线评估血清sCD73、S100A8/A9水平预测患者生存结局的效能。根据ROC曲线分析的最佳截断值将患者分为sCD73高表达组、sCD73低表达组以及S100A8/A9高表达组、S100A8/A9低表达组。采用Cox回归分析影响PD-1/PD-L1抑制剂治疗晚期子宫内膜癌生存预后的因素。分析血清sCD73、S100A8/A9表达水平与患者临床病理特征的关联性。结果 存活组血清sCD73、S100A8/A9水平低于死亡组,差异有统计学意义(P<0.05)。ROC曲线分析结果显示,血清sCD73、S100A8/A9均能有效预测PD-1/PD-L1抑制剂治疗晚期子宫内膜癌患者的生存结局(P<0.05),其最佳截断值分别为5.30μg/L、3.06μg/mL。sCD73、S100A8/A9低表达组的生存预后均优于其高表达组(log-rank检验:χ^(2)=91.367,P<0.001;χ^(2)=69.852,P<0.001)。多因素Cox回归分析结果显示,较高的血清sCD73[HR(95%CI)=2.511(1.497~4.214),P<0.001]、S100A8/A9[HR(95%CI)=1.806(1.106~2.948),P=0.018]水平是患者生存预后不良的独立危险因素。sCD73、S100A8/A9高表达组低分化程度占比显著大于其低表达组(P<0.05)。结论 晚期子宫内膜癌患者血清sCD73、S100A8/A9高水平可能提示其肿瘤分化程度低,是PD-1/PD-L1抑制剂治疗患者生存预后不良的危险因素。

Objective To analyze the correlation of serum soluble CD73(sCD73)and S100 calcium-binding proteins A8/A9(S100A8/A9)levels with clinicopathological features and therapeutic prognosis of programmed death receptor-1(PD-1)/programmed death-ligand 1(PD-L1)inhibitors in patients with advanced endometrial cancer.Methods A total of 142 patients with advanced endometrial cancer who were treated with PD-1/PD-L1 inhibitors in the First Hospital of Qiqihar from March 2020 to February 2021 were recruited.A total of 5 mL of fasting elbow venous blood was collected from the patients in the morning after admission and their blood serum were collected,and the patients′serum levels of sCD73 and S100A8/A9 were detected by using enzyme-linked immunosorbent assay(ELISA).During the follow-up period,58 patients died(death group)and 84 patients survived(survival group).The efficacy of serum sCD73 and S100A8/A9 levels in predicting the patients′survival outcomes were evaluated by using receiver operating characteristic(ROC)curve.According to the optimal cut-off values of the ROC curve analysis,the patients were divided into sCD73 high expression group,sCD73 low expression group,S100A8/A9 high expression group and S100A8/A9 low expression group.The factors affecting the survival prognosis of the advanced endometrial cancer patients treated with PD-1/PD-L1 inhibitors were analyzed by using Cox regression.The correlation of serum sCD73 and S100A8/A9 expression levels with the patients′clinicopathological features were analyzed.Results The serum levels of sCD73 and S100A8/A9 in the survival group were lower than those in the death group,and the differences were statistically significant(P<0.05).The results of ROC curve analysis showed that serum sCD73 and S100A8/A9 could effectively predict the survival outcomes of the advanced endometrial cancer patients treated with PD-1/PD-L1 inhibitors(P<0.05),and the optimal cut-off values were 5.30μg/L and 3.06μg/mL,respectively.The survival prognosis in the sCD73 low expression group and the S100A8/A9 low expression group was better than that in the sCD73 high expression group and the S100A8/A9 high expression group,respectively(log-rank test:χ2=91.367,P<0.001;χ2=69.852,P<0.001).The results of multivariate Cox regression analysis showed that higher serum levels of sCD73[HR(95%CI)=2.511(1.497-4.214),P<0.001]and S100A8/A9[HR(95%CI)=1.806(1.106-2.948),P=0.018]were independent risk factors for poor survival prognosis in the patients.The proportions of poor differentiation in the sCD73 high expression group and the S100A8/A9 high expression group were significantly greater than those in the sCD73 low expression group and the S100A8/A9 low expression group,respectively(P<0.05).Conclusion High levels of serum sCD73 and S100A8/A9 in the patients with advanced endometrial cancer may indicate poor tumor differentiation and are risk factors for poor survival prognosis in the patients treated with PD-1/PD-L1 inhibitors.