CDO1和CELF4基因甲基化在子宫内膜癌筛查中的应用价值

The Application Value of CDO1 and CELF4 Gene Methylation in Endometrial Cancer Screening

摘要: 目的：探讨宫颈脱落细胞中CDO1和CELF4基因甲基化检测技术在子宫内膜癌筛查中的应用价值，并探讨绝经状态及BMI对检测效能的影响。方法：纳入2024年3月~2025年5月于重庆市医科大学附属第一医院就诊疑似子宫内膜病变的145例患者(EC组30例，良性病变组115例)，采用定量甲基化特异性PCR检测CDO1m和CELF4m水平，计算ΔCt值。绘制ROC曲线评估诊断效能，按绝经状态及BMI分层进行亚组分析。采用Logistic回归分析危险因素，Fisher精确检验比较组间差异。结果：共纳入145例患者，收集患者基本信息、肿瘤生物学标记物、子宫内膜厚度、CDO1mΔCt、CELF4mΔCt等，以子宫内膜组织病理学诊断为金标准进行分组，其中子宫内膜癌30例，良性病变组115例。EC组CDO1m和CELF4m水平显著高于良性组(中位数7.45 vs 15.90, 7.65 vs 16.10，均P < 0.001)，而CA125和HE4无显著差异。双基因联合检测AUC为0.958 (95% CI: 0.904~1.000)，敏感度93.3%，特异度97.4%，优于单基因检测。多因素分析显示CDO1m阳性(OR = 368.02, 95% CI: 14.64~9251.20)和CELF4m阳性(OR = 461.29, 95% CI: 22.05~9648.37)均为EC独立危险因素。绝经后亚组(n = 60)中CELF4m表现最优，敏感度88.24%，特异度100%，Youden指数0.882。在BMI ≥ 24 kg/m²亚组中，EC组甲基化阳性率显著高于良性病变组(70.59% vs 3.64%, P < 0.001)。结论：CDO1/CELF4甲基化是EC诊断的有效分子标志物，双基因联合检测效能优异，具有成为子宫内膜癌早期筛查和风险预测分子标志物的潜力。

Abstract: Objective: This paper aims to evaluate the clinical value of CDO1 and CELF4 DNA methylation in the diagnosis of endometrial cancer (EC), and to explore the influence of menopausal status and BMI on detection efficacy. Methods: A total of 145 patients (EC group, n = 30; benign lesion group, n = 115) were enrolled from March 2024 to May 2025. Quantitative methylation-specific PCR was used to detect CDO1m and CELF4m levels, and ΔCt values were calculated. ROC curves were drawn to evaluate diagnostic efficacy. Subgroup analyses were performed according to menopausal status and BMI. Logistic regression was used for risk factor analysis, and Fisher’s exact test was used for group comparison. Results: A total of 145 patients were included. The basic information, tumor biological markers, endometrial thickness, CDO1mΔCt, CELF4mΔCt, etc. were collected. The patients were grouped according to the gold standard of endometrial histopathological diagnosis, including 30 cases of endometrial cancer and 115 cases of benign lesion group. CDO1m and CELF4m levels in the EC group were significantly higher than those in the benign group (median 7.45 vs 15.90, 7.65 vs 16.10, both P < 0.001), while CA125 and HE4 showed no significant differences. The dual-gene combined test showed an AUC of 0.958 (95% CI: 0.904~1.000), with sensitivity of 93.3% and specificity of 97.4%, superior to single-gene tests. Multivariate analysis showed that CDO1m positivity (OR = 368.02, 95% CI: 14.64~9251.20) and CELF4m positivity (OR = 461.29, 95% CI: 22.05~9648.37) were independent risk factors for EC. In the postmenopausal subgroup (n = 60), CELF4m showed optimal performance with sensitivity of 88.24%, specificity of 100%, and Youden index of 0.882. In the BMI ≥ 24 kg/m² subgroup, the methylation-positive rate in the EC group was significantly higher than that in the benign lesion group (70.59% vs. 3.64%, P < 0.001). Conclusions: CDO1/CELF4 methylation is an effective molecular biomarker for the diagnosis of endometrial cancer (EC). The combined detection of the two genes demonstrates excellent diagnostic performance and shows potential as a molecular marker for early screening and risk prediction of endometrial cancer.