Correlation Of DNA-PKcs/ P53 With Radiosensitivity And Prognoses Of Cervical Cancer

Objective: The primary aim of this study was to investigate the association of tumor response to radiotherapy with the expression in cervical cancer of p53 and DNA-depended protein kinase catalytic subunitit (DNA-PKcs) known to be involved in the DNA damage identification and DNA repair after treatment with ionising radiation, and investigate if the expression of p53 and DNA-PKcs in cervical cancer can be used as predictive markers for radiotherapy (RT) response in cervical cancer. Another aim is to identify the correlation between p53 and DNA-PKcs. the third aim is to study if the expression of p53 and DNA-PKcs in cervical cancer correlates with overall survival of patients with cervical cancer,analyze if p53 and DNA-PKcs can be used as prognoses of cervical cancer.Methods: Sixty-three patients, from Liaoning Tumor Hospital, pathologically diagnosed cervical cancer, FIGO-stageⅠB -ⅡB, were divided into two groups according to pathological tumor response to radiation——radioresistant or radiosensitive. All the patients received the same treatment: preoperative 192Ir high-dose-rate intracavitary brachytherapy in 7Gy per fraction once a week. The total dose of 192Ir brachytherapy for all patients was 14Gy to point A (2 cm lateral to the central canal of the uterus and 2 cm up from the mucous membrane of the lateral fornix in the axis of the uterus), followed by radical surgery. After RT, 32 patients demonstrated pathologic radiosensitive, whereas 31 patients demonstrated pathologic radioresistant in the surgical specimen. Formalin-fixed, paraffin-embedded sections (4-um thick) of primary uterine cervical tumor biopsies were investigated by immunohistochemistry. When comparison between high and low protein expression was assessed, a high protein level was defined as a percentage of stained cells above the median value and a low protein level was defined as a percentage of stained cells below the median value. the Expression score of of p53 and DNA-PKcs in primary tumors was respectively compared and analyzed between the two groups with Pearsonχ2test. Correlation coefficient of Spearman (rs) was calculated to compare expression of protein p53 and DNA-PKcs. Survival analysis was also performed. Overall survival was estimated using the Kaplan-Meier method, and differences of survival in the two groups were analyzed using the log-rank test.Results: It was found that tumor-transformed tissue showed positive immunostaining of DNA-PKcs while non-neoplastic squamous epithelium and tumor-free cervix glands showed negative immunoreactivity. The levels of DNA-PKcs were significantly different between the radioresistant group and the radiosensitive one. DNA-PKcs-high-express tumors showed significantly much radioresistant than DNA-PKcs-low-express ones(χ2 =36.444,p <0.001) and the latter has a significantly better overall survival. Positive p53 tumors were significantly more common among radioresistant groups than in radiosensitive groups (χ2 =7.483,p =0.006),there was no significant difference in overall survival between the two groups. Moreover, significant correlation between p53 and DNA-PKcs was also found. ( r =0.276, p =0.029 ,bilateral).Conclusion: DNA-PKcs and p53 could be used as predictive markers for radiotherapy response in cervical cancer, high expression of DNA-PKcs and p53 lead to radioresistance. And the two factors had positive correlation. In addition, overall survival was significantly better in the DNA-PKcs-low-express patients as compared with those who were DNA-PKcs-high-express.