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[DNA甲基化在绝经后妇女子宫内膜癌筛查中的作用]

[The role of DNA methylation in the screening of endometrial cancer in postmenopausal women].

作者信息

Kong L H, Xiao X P, Wan R, Chao X P, Chen X J, Wang J, Wu H W, Li L

机构信息

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.

出版信息

Zhonghua Yi Xue Za Zhi. 2023 Mar 28;103(12):907-912. doi: 10.3760/cma.j.cn112137-20220929-02058.

Abstract

To explore the application value of cervical exfoliated cell DNA methylation (CDO1 and CELF4) combined with or without transvaginal sonography (TVS) for screening endometrial cancer in postmenopausal women. 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. The 143 patients were divided into an endometrial cancer group (=56) and a control group (=87), aged (59.27±6.45) and (61.07±8.26) years, respectively (=0.051). Multivariate logistic regression analysis showed that, CA125≥35 U/ml, postmenopausal bleeding, endometrial thickness≥5 mm, CDO1 ΔCt≤8.4, and CELF4 ΔCt≤8.8 were the risk factors for endometrial cancer, with (95%) of 33.23 (2.51-1 335.28), 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 values0.05). 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%: 75.9%-94.8%) and 90.8% (95%: 82.7%-95.9%), respectively. TVS combined with DNA methylation detection further improved the sensitivity to 100.0% (95%: 93.6%-100.0%), but could not improve the specificity (59.8%, 95%: 48.8%-70.1%). 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.

摘要

探讨宫颈脱落细胞DNA甲基化(CDO1和CELF4)联合或不联合经阴道超声(TVS)在绝经后女性子宫内膜癌筛查中的应用价值。选取2020年5月至2021年10月在北京协和医院妇产科因疑似子宫内膜病变而行宫腔镜检查的143例绝经后女性纳入本研究。在宫腔镜检查前采集宫颈脱落细胞进行基因甲基化检测。同时收集临床资料、肿瘤标志物及TVS检查的子宫内膜厚度。以子宫内膜组织病理学为金标准,采用多因素非条件logistic回归分析子宫内膜癌的危险因素,具体探讨基因甲基化联合或不联合TVS的作用。143例患者分为子宫内膜癌组(n = 56)和对照组(n = 87),年龄分别为(59.27±6.45)岁和(61.07±8.26)岁(P = 0.051)。多因素logistic回归分析显示,CA125≥35 U/ml、绝经后阴道流血、子宫内膜厚度≥5 mm、CDO1 ΔCt≤8.4及CELF4 ΔCt≤8.8是子宫内膜癌的危险因素,OR(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)及44.01(6.79 - 285.25)(均P值<0.05)。双基因甲基化(CDO1或CELF4)筛查子宫内膜癌的敏感度和特异度均高于其他因素,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将敏感度提高至100.0%(95%CI:93.6% - 100.0%),但特异度未提高(59.8%,95%CI:48.8% - 70.1%)。在疑似子宫内膜病变的绝经后女性中,宫颈细胞学DNA甲基化筛查子宫内膜癌的准确性优于其他非侵入性临床指标,DNA甲基化联合TVS可进一步提高筛查敏感度。

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