DNA甲基化检测在育龄期异常子宫出血女性子宫内膜癌诊断中的应用价值  

Application of DNA methylation in detection of endometrial carcinoma in women with abnormal uterine bleeding at childbearing age

作　　者：赵行平 徐大宝[1] 马洁稚[1] 傅英钦 李斌玉 靳希桐 刘禹利 刘沛 Zhao Xingping;Xu Dabao;Ma Jiezhi;Fu Yingqin;Li Binyu;Jin Xitong;Liu Yuli;Liu Pei(Department of Gynecology,the Third Xiangya Hospital of Central South University,Changsha 410000,China;Precision Medicine Center,the First Affiliated Hospital of Guangdong Pharmaceutical University,Guangzhou 510000,China;Beijing Origin-Poly Bio-Tec Co.,Ltd.,Beijing 102600,China)

机构地区：[1]中南大学湘雅三医院妇科,长沙410000 [2]广东药科大学附属第一医院精准医学中心,广州510000 [3]北京起源聚禾生物科技有限公司,北京10260

出　　处：《中华检验医学杂志》2023年第4期367-374,共8页Chinese Journal of Laboratory Medicine

基　　金：国家重点研发计划(2018YFC1004804)。

摘　　要：目的探讨应用宫颈脱落细胞DNA(半胱氨酸双加氧酶1型,CDO1和CUGBP Elav样家族成员4,CELF4)甲基化检测育龄期女性子宫内膜癌的应用价值。方法选取2021年11月至2022年10月就诊于中南大学湘雅三医院妇科异常子宫出血的育龄期、有宫腔镜检查手术指征的女性517例进行前瞻性研究,术前收集宫颈脱落细胞进行细胞学、人类乳头瘤病毒(HPV)和DNA甲基化检测。同时收集患者基本临床信息、生物标记物与经阴道超声(TVS)子宫内膜厚度等信息。以宫腔镜下内膜组织病理学诊断为金标准,采用单因素Logistic回归分析子宫内膜癌的高危因素,利用受试者工作特征曲线下面积(AUC)分析DNA甲基化检测对育龄期女性子宫内膜癌的检测效能。结果年龄、体重指数(BMI)≥25 kg/m^(2)、内膜厚度≥11 mm、CDO1^(m)ΔCt≤8.4、CELF4^(m)ΔCt≤8.8、双基因甲基化与年轻女性子宫内膜癌的发生相关,OR值(95%CI)分别为1.16(1.08~1.25)、4.33(1.89~10.31)、9.49(3.88~26.69)、69.62(25.70~224.36)、23.64(9.66~63.99)、87.39(24.83~555.05),均P<0.05。在这些检测方案中,CDO1^(m)/CELF4^(m)甲基化诊断子宫内膜癌的AUC最高为0.90(95%CI 0.83~0.97),其敏感度、特异度分别为91.7%(95%CI 80.6%~100%)和88.8%(95%CI 86.0%~91.6%)。TVS联合DNA甲基化检测可进一步提高敏感度至95.8%(95%CI 87.8%~100%),但特异度为68.0%(95%CI 63.8%~72.1%)。结论对于育龄期女性中异常子宫出血或阴道异常排液的女性,宫颈细胞学DNA甲基检测子宫内膜癌的准确性优于其他无创临床方案。DNA甲基化联合TVS可以改善检测的敏感性。Objective This work aims to explore the application value of cervical exfoliated cell DNA(Cysteine dioxygenase type 1,CDO1 and CUGBP Elav-like family member 4,CELF4)methylation in the detection of endometrial cancer in women of childbearing age.Methods From November 2021 to October 2022,a prospective study was conducted on a total number of 517 reproductive-age women with abnormal uterine bleeding who had surgical indications for hysteroscopy at the Xiangya Third Hospital of Central South University.The cervical exfoliated cells were collected for cytology,HPV(human papillomavirus)and gene methylation detection before operation.Clinical information of patients,level of tumor-related biomarkers,and endometrial thickness of transvaginal ultrasound(TVS)were also collected.Single factor regression method was used to analyze the high-risk factors of endometrial cancer.Receiver operating characteristic curve analysis was used to obtain the area under the curve(AUC),focusing on the screening efficacy of gene methylation test for endometrial cancer in women of childbearing age.Results The age,body mass index(BMI)≥25 kg/m^(2),endometrial thickness≥11 mm,CDO1^(m)ΔCt≤8.4,CELF4^(m)ΔCt≤8.8,and double gene methylation were associated with endometrial cancer in women of childbearing age,1.16(1.08-1.25),4.33(1.89-10.31),9.49(3.88-26.69),69.62(25.70-224.36),23.64(9.66-63.99),87.39(24.83-555.05),all P<0.05.The AUC was 0.90(95%CI 0.83-0.97)of CDO1^(m)/CELF4^(m)in diagnosing endometrial carcinoma was higher than others factors,with sensitivity and specificity of 91.7%(95%CI 80.6%-100%)and 88.8%(95%CI 86.0%-91.6%).TVS combined with DNA methylation detection further improved the sensitivity to 95.8%(95%CI 87.8%-100%),but could not improve the specificity 68.0%(95%CI 63.8%-72.1%).Conclusions For women of childbearing age with abnormal uterine bleeding or abnormal vaginal discharge,the accuracy of cervical cytology DNA methyl detection of endometrial cancer is better than other non-invasive clinical programs.DNA methylation co

关 键 词：子宫不规则出血 子宫内膜肿瘤 早癌诊断 DNA甲基化 超声检查 

分 类 号：R737.33[医药卫生—肿瘤]