IER5 as a promising predictive marker promotes irradiation-induced apoptosis in cervical cancer tissues from patients undergoing chemoradiotherapy

Abstract

// Yang Liu 1 , Ming Tian 1 , Hui Zhao 1 , Yue He 1 , Fengshuang Li 1 , Xiunan Li 1 , Xinping Yu 1 , Kuke Ding 3 , Pingkun Zhou 2 , Yumei Wu 1 1 Department of Gynecologic Oncology, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing 100006, P.R.China 2 Department of Radiation Toxicology and Oncology, Institute of Radiation Medicine, Academy of Military Medical Sciences, Beijing 100850, P.R. China 3 National Institute for Radiological Protection, Chinese Center for Disease Control and Prevention, Beijing 100088, P.R. China Correspondence to: Yumei Wu, email: wym597118@163.com Keywords: IER5, cervical cancer, radiosensitivity, apoptosis, biomarker Received: December 20, 2016      Accepted: March 28, 2017      Published: April 05, 2017 ABSTRACT Purpose: To define the role of immediate-early 5 (IER5) gene as a promising biomarker in predicting the radiosensitivity and prognosis of cervical cancer patients receiving cisplatin-based concurrent chemoradiotherapy (DDP-CCRT). Results: Our investigations found that IER5 level was markedly elevated in cervical cancer patients after being treated with irradiation, which indicated IER5 was closely dose induced. By contrast, the correlation between IER5 and radiosensitivity cannot be confirmed by the present study. The up-regulation of IER5 expression effectively increased cell apoptosis after administration of irradiation ( P < 0.05). Using an ANOVA model for repeated-measures, we found significant association between the IER5 level and tumor size ( P < 0.05). Materials and Methods: Forty-three cervical cancer patients stage II b -III b received DDP-CCRT were registered. Biopsy tissues were obtained after administration of irradiation dose of 0 Gy, 2~6 Gy, 10 Gy, 20 Gy, 30 Gy, respectively. The IER5 protein and mRNA levels were measured by immunohistochemistry, western blot and quantitative polymerase chain reaction, respectively; besides, the apoptosis rate was assessed by transferase-mediated dUTP nick end labeling. Conclusions: Mechanistically, we confirmed that IER5 induced by radiation dose enhanced apoptosis of cervical cancer, was inversely associated with tumor size. In conclusion, our studies indicate target IER5 is improved to be a potential radiosensitizer for developing effective therapeutic strategies against cervical cancer to radiotherapy and a predictive biomarker for radiosensitivity.