J Cancer 2021; 12(17):5136-5143. doi:10.7150/jca.57460 This issue

Research Paper

Methylation of PAX1 gene promoter in the prediction of concurrent chemo-radiotherapy efficacy in cervical cancer

Xuanxuan Li1, Xue. Zhou1, Manting Zeng1, Yangying Zhou1, Yu Zhang2, Yu-Ligh Liou3✉, Hong Zhu1✉

1. Department of Oncology, Xiangya Hospital, Central South University, Hunan 410008 China.
2. Department of Obstetrics and Gynecology, Xiangya Hospital, Central South University, Hunan 410008 China.
3. Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Hunan 410008 China.

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Citation:
Li X, Zhou X, Zeng M, Zhou Y, Zhang Y, Liou YL, Zhu H. Methylation of PAX1 gene promoter in the prediction of concurrent chemo-radiotherapy efficacy in cervical cancer. J Cancer 2021; 12(17):5136-5143. doi:10.7150/jca.57460. Available from https://www.jcancer.org/v12p5136.htm

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Abstract

Graphic abstract

Objectives: Cervical cancer is the fourth leading cause of cancer death among women worldwide. In currently, aberrant methylation of PAX1 is found in variety of solid tumors, including cervical cancer. In addition, the role of PAX1 gene methylation in cervical cancer and precancerous lesions screening has been confirmed in previous study. Here, we evaluated the predictive value of PAX1 methylation in concurrent chemo-radiotherapy (CCRT) outcomes in cervical cancer.

Methods: This study enrolled 82 cervical cancer patients from August 2018 to August 2020. We compared the clinical results between different PAX1 methylation status. Hyper-methylation patients were subjects to MRI and quantitative methylation-specific PCR (QMSP) for PAX1 before, in the middle, immediately after, 1 month and 3 months after CCRT. The changes in PAX1 methylation during CCRT were analyzed.

Results: The lower PAX1 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 PAX1 △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 PAX1 △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.

Conclusion: The PAX1 methylation level may predict the sensitivity and efficacy of CCRT in cervical cancer.

Keywords: Cervical cancer, PAX1, DNA methylation, Current chemo-radiotherapy, Biomarkers