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宫颈癌脱落细胞RBL1启动子甲基化与患者放疗抵抗的关系
作者:霍叶琳1  王月2  房国涛2 
单位:1. 保定市第一医院 妇产科, 河北 保定 071000;
2. 河北大学附属医院 肿瘤科, 河北 保定 071000
关键词:宫颈癌 放疗抵抗 视网膜母细胞瘤样蛋白1 甲基化 宫颈脱落细胞 
分类号:R737.33
出版年·卷·期(页码):2022·41·第二期(198-203)
摘要:

目的:探究宫颈癌脱落细胞视网膜母细胞瘤样蛋白1(RBL1)启动子甲基化状态与宫颈癌患者放疗抵抗的相关性。方法:选取2015年5月至2017年4月间保定市第一医院收治的82例宫颈癌患者,接受同步放化疗一线治疗。分别于放疗前(T0)、放疗中期(T1)、放疗结束(T2)采用定量甲基化特异性PCR法检测宫颈脱落细胞RBL1基因启动子甲基化扩增曲线交叉点变化值(ΔCp值)。根据监测3个月的治疗反应,获得完全缓解或部分缓解者纳入敏感组,否则纳入抵抗组。采用多因素Logistic回归模型和受试者工作特征(ROC)曲线分析RBL1基线甲基化对放疗抵抗的预测价值。结果:抵抗组患者各时间点RBL1基因启动子甲基化ΔCp值均低于敏感组(P<0.001),T1、T2时的ΔCp值较基线值变化率均大于敏感组(P<0.001)。RBL1基线启动子甲基化是影响宫颈癌患者产生放疗抵抗的独立危险因素(P<0.05),其ΔCp值预测宫颈癌患者产生放疗抵抗的ROC曲线下面积为0.794(95%CI为0.697~0.892)。结论:RBL1启动子甲基化与宫颈癌患者放疗抵抗有关,监测RBL1甲基化的动态变化有助于优化宫颈癌的个体化治疗方案。

Objective: To investigate the correlation between the retinoblastoma-like 1(RBL1) promoter methylation status of exfoliated cervical cancer cells and radioresistance in patients with cervical cancer. Methods: From May 2015 to April 2017, 82 patients with cervical cancer admitted to Baoding First Hospital were selected and treated with concurrent chemo-radiotherapy as the first-line schedule. The crossing point change value of amplification curve(ΔCp) of RBL1 gene promoter methylation before radiotherapy(T0), at medium-term(T1) and at the end(T2) of radiotherapy were detected by quantitative methylation-specific PCR respectively. Patients were followed up for 3 months to monitor treatment response. Patients with completed response or partial response were selected as sensitivity group while those without any response were enrolled in resistance group. Multivariate Logistic regression model and receiver operating characteristic(ROC) curve were used to analyze the predictive value of baseline RBL1 methylation on the radioresistance. Results: The RBL1 gene promoter methylation ΔCp in the resistance group was lower than that in the sensitive group at each time point(P<0.001). And the change rate of ΔCp from baseline at T1 and T2 in the resistant group was higher than that in the sensitive group(P<0.001). The baseline hypermethylation of RBL1 promoter was independent risk factor for radiotherapy resistance in patients with cervical cancer(P<0.05). The area under ROC curve of baseline RBL1 promoter methylation ΔCp for predicting the radiotherapy resistance was 0.794(95%CI0.697-0.892). Conclusion: The RBL1 gene promoter methylation status is related to radiotherapy sensitivity in patients with cervical cancer. Monitoring the dynamic changes of RBL1 methylation is helpful to optimize individualized treatment.

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