血清游离DNA ATM启动子甲基化对局部晚期宫颈鳞癌患者放射抗性的预测价值-东南大学学报医学版

血清游离DNA ATM启动子甲基化对局部晚期宫颈鳞癌患者放射抗性的预测价值

单位：南通大学附属肿瘤医院妇瘤科, 江苏南通 226000

关键词：血清游离DNA 共济失调毛细血管扩张突变基因甲基化局部晚期宫颈鳞癌调强放疗

分类号：R737.33

出版年·卷·期（页码）：2023·42·第一期（116-124）

摘要：

目的：探讨血清游离DNA （cfDNA）共济失调毛细血管扩张突变基因（ATM）启动子甲基化对局部晚期宫颈鳞癌（CSCC）患者放射抗性的预测价值。方法：选取2016年3月至2020年7月在本院完成调强放疗的144例局部晚期CSCC患者作为研究对象。采用定量甲基化特异性聚合酶链反应法检测血清cfDNA ATM启动子甲基化水平，并收集随访数据。放疗完成1个月后根据实体瘤疗效评价标准评估患者治疗反应。结果：局部晚期CSCC患者治疗前血清cfDNA ATM启动子甲基化水平为66.15%（51.28%，76.28%），与主要临床特征无关（P>0.05）。抵抗组局部晚期CSCC患者治疗前血清cfDNA ATM启动子甲基化水平显著低于敏感组（P<0.001）。血清cfDNA ATM启动子甲基化预测局部晚期CSCC患者放射抗性的ROC曲线下面积为0.798（95%CI：0.723~0.873）。Logistic回归分析显示，治疗前血清cfDNA ATM启动子甲基化水平是局部晚期CSCC患者放射抗性的独立预测因子（P<0.05）。预后分析显示血清cfDNA ATM启动子甲基化是局部晚期CSCC患者的独立有利预后因素（P<0.05）。局部晚期CSCC患者血清cfDNA ATM启动子甲基化高水平组术后无进展生存期、总生存期、远处无转移生存期和局部无进展生存期均显著优于低水平组（P<0.05）。结论：治疗前血清cfDNA ATM启动子甲基化状态可能是预测局部晚期CSCC患者放疗后预后的有用生物标志物。

Objective: To investigate the predictive value of serum cell-free DNA(cfDNA) ataxia-telangiectasia mutated gene(ATM) promoter methylation for radioresistance in patients with locally advanced cervical squamous cell carcinoma(CSCC). Methods: A total of 144 patients with locally advanced CSCC who completed intensity modulated radiotherapy in our hospital from March 2016 to July 2020 were selected as the research objects. Quantitative methylation-specific polymerase chain reaction was used to detect the methylation level of ATM promoter in serum cfDNA, and follow-up data were collected. One month after the completion of radiotherapy, the treatment response was evaluated according to response evaluation criteria in solid tumours. Results: The serum cfDNA ATM promoter methylation level in patients with locally advanced CSCC before treatment was 66.15%(51.28%, 76.28%), which was not related to the main clinical characteristics(P>0.05). The methylation level of ATM promoter of cfDNA in the resistant group was significantly lower than that in the sensitive group before treatment(P<0.001). The area under the ROC curve of serum cfDNA ATM promoter methylation in predicting radioresistance in patients with locally advanced CSCC was 0.798(95%CI: 0.723-0.873). Logistic regression analysis showed that serum cfDNA ATM promoter methylation level before treatment was an independent predictor of radioresistance in patients with locally advanced CSCC(P<0.05). Prognostic analysis showed that methylation of serum cfDNA ATM promoter was an independent prognostic factor in locally advanced CSCC patients(P<0.05). The progression-free survival, overall survival, distant metastasis-free survival and local progression-free survival of patients with locally advanced CSCC were significantly better in the high level of serum cfDNA ATM methylation group than in the low level group(P<0.05). Conclusion: The methylation status of serum cfDNA ATM promoter before treatment may be a useful biomarker for predicting the prognosis of locally advanced CSCC patients after radiotherapy.

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