血清人附睾蛋白-4在预测早期子宫内膜癌和非典型子宫内膜增生宫内孕激素治疗反应方面的临床意义

Clinical significance of serum human epididymis protein-4 in predicting response to intrauterine progestin therapy in early endometrial carcinoma and atypical endometrial hyperplasia

目的评估血清人附睾蛋白-4(HE4)预测早期子宫内膜癌(EC)和非典型子宫内膜增生(AEH)宫内孕激素治疗反应的价值。方法回顾性分析2019年5月至2022年6月确诊的100例低级别早期EC患者及100例AEH患者。所有患者均采用左炔诺孕酮宫内节育系统进行宫内孕激素治疗。治疗12个月时,达到完全缓解及部分缓解的患者被视为有反应者(反应组,n=138),而疾病稳定及疾病进展的患者被视为无反应者(无反应组,n=62)。采用全自动采用化学发光酶免疫分析法检测基线和治疗3个月时的血清HE4水平。结果无反应组患者的基线血清HE4水平显著高于反应组(P<0.001)。基线血清HE4水平预测患者LNG-IUS治疗无反应的受试者操作特征曲线下面积为0.775(95%CI:0.711~0.831),基线血清HE4水平>42.10 pmol/L时,灵敏度为83.87%,特异度为60.14%。经单因素及多因素Logistic回归分析,基线血清HE4水平>42.10 pmol/L为患者LNG-IUS治疗无反应的独立危险因素(P<0.001)。无反应组治疗3个月时的血清HE4水平仍高于反应组(P<0.001)。无反应组患者治疗3个月时的血清HE4水平与基线比较,差异无统计学意义(P=0.149),而反应组患者治疗3个月时的血清HE4水平明显降低(P<0.001)。此外,无反应组患者治疗3个月时血清HE4水平增加百分比也高于反应组(P=0.003)。结论基线血清HE4高水平与AEH和低级别早期EC患者的LNG-IUS治疗无反应独立相关。

Objective To estimate the value of serum human epididymis protein 4(HE4)predict early endometrial carcinoma(EC)and atypical endometrial hyperplasia(AEH)in the prediction of the intrauterine pregnancy hormone treatment response.Methods A retrospective analysis was conducted including 100 cases of low-grade early EC patients and 100 cases of patients with AEH confirmed from May 2019 to June 2022.All patients were treated with intrauterine progesterone using the levonorgestrel intrauterine system.At 12 months of treatment,patients with complete and partial responses were considered responsive(response group,n=138),while patients with stable and progressive disease were considered non-responsive(non-response group,n=62).Serum HE4 levels were measured at baseline and at 3 months of treatment using a fully automated chemiluminescent enzyme immunoassay.Results The baseline serum HE4 level in non-respond group was significantly higher than that in respond group(P<0.001).Baseline serum HE4 levels predict LNG-IUS treatment without reaction area under the receiver operating characteristic curve was 0.775(95%CI:0.711‒0.831),baseline serum HE4 level>42.10 pmol/L,the sensitivity was 83.87%,specificity of 60.14%.Univariate and multifactorial Logistics regression analysis showed that baseline serum HE4 level>42.10 pmol/L was an independent risk factor for non-response to LNG-IUS treatment(P<0.001).The non-respond group still had a significantly higher serum HE4 level than the respond group after 3 months of treatment(P<0.001).There was no significant difference in serum HE4 level in the no-response group after 3 months of treatment compared with baseline(P=0.149),while the serum HE4 level in the response group after 3 months of treatment was significantly decreased(P<0.001).In addition,the percentage increase of serum HE4 level at 3 months of treatment in the no-response group was also higher than that in the response group(P=0.003).Conclusion High serum HE4 levels at baseline were independently associated with non-respond to LNG-IUS therapy in patients with AEH and low-grade early EC.