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基因启动子甲基化在宫颈癌同步放化疗疗效预测中的作用

Methylation of gene promoter in the prediction of concurrent chemo-radiotherapy efficacy in cervical cancer.

作者信息

Li Xuanxuan, Zhou Xue, Zeng Manting, Zhou Yangying, Zhang Yu, Liou Yu-Ligh, Zhu Hong

机构信息

Department of Oncology, Xiangya Hospital, Central South University, Hunan 410008 China.

Department of Obstetrics and Gynecology, Xiangya Hospital, Central South University, Hunan 410008 China.

出版信息

J Cancer. 2021 Jun 22;12(17):5136-5143. doi: 10.7150/jca.57460. eCollection 2021.

Abstract

Cervical cancer is the fourth leading cause of cancer death among women worldwide. In currently, aberrant methylation of is found in variety of solid tumors, including cervical cancer. In addition, the role of gene methylation in cervical cancer and precancerous lesions screening has been confirmed in previous study. Here, we evaluated the predictive value of methylation in concurrent chemo-radiotherapy (CCRT) outcomes in cervical cancer. This study enrolled 82 cervical cancer patients from August 2018 to August 2020. We compared the clinical results between different methylation status. Hyper-methylation patients were subjects to MRI and quantitative methylation-specific PCR (QMSP) for before, in the middle, immediately after, 1 month and 3 months after CCRT. The changes in methylation during CCRT were analyzed. The lower methylation status were related to a poor tumor response. Based on the MRI findings three months post-treatment, the hypermethylated patients were classified into the complete response (CR; n=50) and partial remission (PR; n=18) groups. The average △Cp value of CR and PR groups before radiotherapy was 5.08±1.98 and 4.32±2.00 respectively, and after concurrent chemo-radiotherapy was significantly increased to 17.35±4.96 and 16.99±6.17, respectively (P<0.05). Furthermore, the △Cp value between CR and PR groups were significantly different at mid-treatment and performed well in predicting short-term efficacy (AUC 0.84) in this period, and its sensitivity and specificity for predicting PR were 0.72 and 0.88, respectively. The methylation level may predict the sensitivity and efficacy of CCRT in cervical cancer.

摘要

宫颈癌是全球女性癌症死亡的第四大主要原因。目前,在包括宫颈癌在内的多种实体瘤中均发现了异常甲基化。此外,先前的研究已证实基因甲基化在宫颈癌及癌前病变筛查中的作用。在此,我们评估了甲基化在宫颈癌同步放化疗(CCRT)疗效中的预测价值。本研究纳入了2018年8月至2020年8月期间的82例宫颈癌患者。我们比较了不同甲基化状态之间的临床结果。对甲基化程度高的患者在CCRT前、治疗中期、治疗刚结束后、治疗后1个月和3个月进行甲基化定量特异性PCR(QMSP)检测及MRI检查。分析了CCRT期间甲基化的变化情况。甲基化程度较低与肿瘤反应较差有关。根据治疗后三个月的MRI检查结果,将甲基化程度高的患者分为完全缓解(CR;n = 50)组和部分缓解(PR;n = 18)组。放疗前CR组和PR组的平均△Cp值分别为5.08±1.98和4.32±2.00,同步放化疗后分别显著升高至17.35±4.96和16.99±6.17(P<0.05)。此外,CR组和PR组在治疗中期的△Cp值存在显著差异,在此期间对短期疗效的预测表现良好(AUC为0.84),其预测PR的敏感性和特异性分别为0.72和0.88。甲基化水平可能预测宫颈癌CCRT的敏感性和疗效。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e4b/8317535/86eb853689cb/jcav12p5136g001.jpg

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