DNA 甲基化检测是筛查绝经前异常子宫出血妇女子宫内膜癌的重要生物标志物。

DNA methylation detection is a significant biomarker for screening endometrial cancer in premenopausal women with abnormal uterine bleeding.

机构信息

Gynecology, the Third Xiangya Hospital, Central South University, Changsha, Hunan, China.

Jiangwan Research Institute, Central South University, Changsha, Hunan, China.

出版信息

Int J Gynecol Cancer. 2024 Aug 5;34(8):1165-1171. doi: 10.1136/ijgc-2024-005723.

DOI:10.1136/ijgc-2024-005723

PMID:39043572

Abstract

OBJECTIVE

The aim of our study was to explore the value of DNA (CDO1m/CELF4m) methylation detection in exfoliated cervical cells collected for screening endometrial cancer in premenopausal women with abnormal uterine bleeding.

METHODS

A total of 296 premenopausal women with abnormal uterine bleeding admitted to the Department of Obstetrics and Gynecology at the Third Xiangya Hospital of Central South University from November 2021 to October 2022 were selected. Clinical characteristics, endometrial thickness measured by transvaginal ultrasound and serum CA125 were collected. Exfoliated cervical cells from the thinPrep cytogic test were collected for DNA (CDO1m/CELF4m) methylation testing. Endometrial tissue was collected under hysteroscopy for pathological diagnosis as the gold standard. A univariate logistic regression model was used to analyze risk factors for endometrial cancer. The receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to measure the diagnostic efficacy of DNA methylation detection in endometrial cancer screening of women with abnormal uterine bleeding.

RESULTS

Univariate logistic regression analysis showed that age, body mass index (BMI) ≥25 kg/m, endometrial thickness ≥11 mm, CDO1 methylation (CDO1mΔCt≤8.4), CELF4 methylation (CELF4mΔCt≤8.8), and dual gene methylation (CDO1mΔCt≤8.4 or CELF4mΔCt≤8.8) were independent risk factors for endometrial cancer in women with abnormal uterine bleeding. The odds ratio (OR) values (95% confidence interval (CI) were 0.87 (0.80-0.95), 4.76 (1.89-11.96), 8.41 (3.13-22.59), 64.49 (20.46-203.33), 12.79 (4.91-33.30), and 42.53 (11.90-152.04), respectively. Among these indicators, dual gene methylation had the higher sensitivity and specificity for endometrial cancer screening (85.7% and 87.6%). Moreover, dual gene methylation combined with BMI or endometrial thickness could further improve the screening efficiency of endometrial cancer in women with abnormal uterine bleeding.

CONCLUSIONS

In premenopausal women with abnormal uterine bleeding, the clinical efficacy of DNA (CDO1m/CELF4m) methylation detection in exfoliated cervical cells for endometrial cancer screening was better than that of other noninvasive clinical indicators. In addition, dual gene methylation combined with BMI or endometrial thickness was a good predictor of endometrial cancer screening.

摘要

目的

本研究旨在探讨在因异常子宫出血就诊的绝经前妇女中，脱落宫颈细胞中 DNA（CDO1m/CELF4m）甲基化检测用于筛查子宫内膜癌的价值。

方法

选取 2021 年 11 月至 2022 年 10 月中南大学湘雅三医院妇产科收治的 296 例因异常子宫出血就诊的绝经前妇女。收集临床特征、经阴道超声测量的子宫内膜厚度和血清 CA125。采用 ThinPrep 液基细胞学检测收集脱落的宫颈细胞进行 DNA（CDO1m/CELF4m）甲基化检测。宫腔镜下采集子宫内膜组织作为金标准进行病理诊断。采用单因素 logistic 回归模型分析子宫内膜癌的危险因素。采用受试者工作特征（ROC）曲线和曲线下面积（AUC）评估 DNA 甲基化检测在异常子宫出血妇女子宫内膜癌筛查中的诊断效能。

结果

单因素 logistic 回归分析显示，年龄、体质量指数（BMI）≥25kg/m²、子宫内膜厚度≥11mm、CDO1 甲基化（CDO1mΔCt≤8.4）、CELF4 甲基化（CELF4mΔCt≤8.8）和双基因甲基化（CDO1mΔCt≤8.4 或 CELF4mΔCt≤8.8）是绝经前妇女异常子宫出血发生子宫内膜癌的独立危险因素。其比值比（OR）值（95%置信区间（CI）分别为 0.87（0.80-0.95）、4.76（1.89-11.96）、8.41（3.13-22.59）、64.49（20.46-203.33）、12.79（4.91-33.30）和 42.53（11.90-152.04）。在这些指标中，双基因甲基化对子宫内膜癌筛查的敏感性和特异性更高（85.7%和 87.6%）。此外，双基因甲基化联合 BMI 或子宫内膜厚度可进一步提高绝经前妇女异常子宫出血子宫内膜癌的筛查效率。