摘要
目的探讨DNA甲基化检测在绝经后女性子宫内膜癌筛查中的应用价值。方法选取2020年5月至2021年10月就诊于北京协和医院妇产科、可疑内膜病变、拟行宫腔镜检查的绝经女性143例,术前收集宫颈脱落细胞进行基因甲基化检测。同时收集患者基本临床信息、生物标记物与经阴道超声(TVS)的子宫内膜厚度等。以宫腔镜下内膜组织病理学诊断为金标准,采用多因素logistic回归模型分析子宫内膜癌的相关因素,利用受试者工作特征(ROC)曲线下的面积(AUC)重点分析基因甲基化检测联合或不联合超声检查对绝经后妇女子宫内膜癌的筛查效能。结果143例患者分为内膜癌组(56例)和对照组(87例),年龄分别为(59.27±6.45)和(61.07±8.26)岁(P=0.051)。多因素分析发现,CA125≥35 U/ml、绝经出血、绝经内膜厚度≥5 mm、CDO1甲基化(ΔCt≤8.4)、CELF4甲基化(ΔCt≤8.8)是发生子宫内膜癌的相关因素,OR值(95%CI)分别为33.23(2.51~1335.28)、8.41(1.81~39.05)、14.45(2.35~88.84)、17.34(3.34~89.98)、44.01(6.79~285.25),均P<0.05。双基因甲基化(CDO1ΔCt≤8.4或CELF4ΔCt≤8.8)诊断内膜癌的灵敏度、特异度最高,分别为87.5%(95%CI:75.9%~94.8%)和90.8%(95%CI:82.7%~95.9%)。TVS联合DNA甲基化检测可进一步提高灵敏度,为100.0%(95%CI:93.6%~100.0%),但不能改善特异度,为59.8%(95%CI:48.8%~70.1%)。结论对于绝经后女性宫颈细胞学DNA甲基化筛查内膜癌的准确性优于其他无创临床方案。联合TVS可以改善筛查的敏感性。
Objective To explore the application value of cervical exfoliated cell DNA methylation(CDO1^(m)and CELF4^(m))combined with or without transvaginal sonography(TVS)for screening endometrial cancer in postmenopausal women.Methods A total of 143 postmenopausal women who underwent hysteroscopy for suspected endometrial lesions in the Department of Obstetrics and Gynecology of Peking Union Medical College Hospital from May 2020 to October 2021 were enrolled in this study.The cervical exfoliated cells were collected for gene methylation before hysteroscopy.Clinical information,tumor biomarkers,and endometrial thickness of TVS were also collected.With endometrial histopathology as the gold standard,multivariate unconditional logistic regression was applied to analyze the risk factors of endometrial cancer.The role of gene methylation with or without TVS were specifically explored.Results The 143 patients were divided into an endometrial cancer group(n=56)and a control group(n=87),aged(59.27±6.45)and(61.07±8.26)years,respectively(P=0.051).Multivariate logistic regression analysis showed that,CA125≥35 U/ml,postmenopausal bleeding,endometrial thickness≥5 mm,CDO1^(m)ΔCt≤8.4,and CELF4^(m)ΔCt≤8.8 were the risk factors for endometrial cancer,with OR(95%CI)of 33.23(2.51-1335.28),8.41(1.81-39.05),14.45(2.35-88.84),17.34(3.34-89.98),and 44.01(6.79-285.25),respectively(all P values<0.05).The sensitivity and specificity of dual-gene methylation(CDO1 or CELF4)in the screening of endometrial carcinoma were both higher than others factors,reaching 87.5%(95%CI:75.9%-94.8%)and 90.8%(95%CI:82.7%-95.9%),respectively.TVS combined with DNA methylation detection further improved the sensitivity to 100.0%(95%CI:93.6%-100.0%),but could not improve the specificity(59.8%,95%CI:48.8%-70.1%).Conclusions In postmenopausal women with suspected endometrial lesions,the accuracy of cervical cytology DNA methylation is better than other noninvasive clinical indicators for the screening of endometrial cancer.DNA methylation combined with TVS can further improve the sensitivity of screening.
作者
孔令华
肖晓萍
万茹
钞晓培
陈晓静
王婧
吴焕文
李雷
Kong Linghua;Xiao Xiaoping;Wan Ru;Chao Xiaopei;Chen Xiaojing;Wang Jing;Wu Huanwen;Li Lei(Department of Obstetrics and Gynecology,National Clinical Research Center for Obstetric&Gynecologic Diseases,Peking Union Medical College Hospital,Beijing 100730,China;Department of Pathology,Peking Union Medical College Hospital,Beijing 100730,China)
出处
《中华医学杂志》
CAS
CSCD
北大核心
2023年第12期907-912,共6页
National Medical Journal of China
基金
中国医学科学院中央级公益性科研院所基本科研业务费专项资金(2020-PT320-003)
北京市科技委员会首都临床诊疗技术研究及转化应用(Z211100002921068)
中央高水平医院临床科研专项(2022-PUMCH-A-117)
关键词
子宫内膜癌
癌症早筛
DNA甲基化
经阴道超声
异常子宫出血
Endometrial cancer
Early cancer screening
DNA methylation
Transvaginal sonography
Abnormal uterine bleeding
作者简介
通信作者:李雷,Email:lileigh@163.com
