诊断为子宫内膜癌(EC)IAG1期或非典型子宫内膜增生(AEH)患者的观察性队列研究,接受器官保存治疗,进行了。
目的:测定早期子宫内膜癌和非典型性增生标本中CDO1、PITX2和CDH13基因甲基化水平,这些标本在器官保留治疗前对激素治疗反应充分和反应不足的患者中获得。
方法:在诊断性清宫术期间,在EC(n=28)和AEH(n=13)的女性中,共获得41个子宫内膜标本,愿意保留生殖功能,进行了研究;该研究包括来自绝经前后和绝经后早期妇女(对照组)的18例子宫癌IAG1期标本。对照组包括18例健康妇女的子宫内膜标本,这些子宫内膜标本是通过诊断性清宫术获得的,用于稽留流产和/或宫腔粘连。使用改进的MS-HRM方法分析甲基化水平。
结果:所有13名AEH患者对药物治疗有完全反应(CR)。在接受子宫癌IAG1期器官保留治疗的组中(n=28),14例患者有完全反应(ECCR组),14例无反应(EC非CR组)。发现除ECCR组(p=0.21)外,所有组的CDO1基因甲基化水平与对照组相比具有统计学上的显著差异(p<0.001)。ECCR和EC非CR组之间的差异的p值<0.001。对照组和研究组之间PITX2基因甲基化水平的差异也有显著差异(p<0.001),除了AEH组(p=0.21)。对于ECCR和EC非CR组之间的差异,p值为0.43。对于CDH13基因甲基化水平,对照组和EC非CR组之间存在统计学上的显着差异(p<0.001),以及对照组和EC比较组(p=0.005)。当比较ECCR组与EC非CR组时,该基因的p值<0.001。CDO1和CDH13基因甲基化的同时评估允许ECCR和EC非CR组之间的准确区分(AUC=0.96)。
结论:评估子宫内膜癌患者(IA期G1)的子宫内膜标本中CDO1和CDH13基因甲基化,计划接受治疗,可以预测治疗结果。
An observational cohort study of patients diagnosed with endometrial cancer (EC) stage IA G1, or atypical endometrial hyperplasia (AEH), undergoing organ-preserving treatment, was conducted.
OBJECTIVE: To determine CDO1, PITX2, and CDH13 gene methylation levels in early endometrial cancer and atypical hyperplasia specimens obtained before organ-preserving treatment in the patients with adequate response and with insufficient response to hormonal treatment.
METHODS: A total of 41 endometrial specimens obtained during diagnostic uterine curettage in women with EC (n = 28) and AEH (n = 13), willing to preserve reproductive function, were studied; 18 specimens of uterine cancer IA stage G1 from peri- and early postmenopausal women (comparison group) were included in the study. The control group included 18 endometrial specimens from healthy women obtained by diagnostic curettage for missed abortion and/or intrauterine adhesions. Methylation levels were analyzed using the modified MS-HRM method.
RESULTS: All 13 women with AEH had a complete response (CR) to medical treatment. In the group undergoing organ-preserving treatment for uterine cancer IA stage G1 (n = 28), 14 patients had a complete response (EC CR group) and 14 did not (EC non-CR group). It was found that all groups had statistically significant differences in CDO1 gene methylation levels compared to the control group (p < 0.001) except for the EC CR group (p = 0.21). The p-value for the difference between EC CR and EC non-CR groups was <0.001. The differences in PITX2 gene methylation levels between the control and study groups were also significantly different (p < 0.001), except for the AEH group (p = 0.21). For the difference between EC CR and EC non-CR groups, the p-value was 0.43. For CDH13 gene methylation levels, statistically significant differences were found between the control and EC non-CR groups (p < 0.001), and the control and EC comparison groups (p = 0.005). When comparing the EC CR group with EC non-CR group, the p-value for this gene was <0.001. The simultaneous assessment of CDO1 and CDH13 genes methylation allowed for an accurate distinction between EC CR and EC non-CR groups (AUC = 0.96).
CONCLUSIONS: The assessment of CDO1 and CDH13 gene methylation in endometrial specimens from patients with endometrial cancer (IA stage G1), scheduled for medical treatment, can predict the treatment outcome.