Oncotarget

Clinical Research Papers:

XRCC2 as a predictive biomarker for radioresistance in locally advanced rectal cancer patients undergoing preoperative radiotherapy

Chang-Jiang Qin, Xin-Ming Song _, Zhi-Hui Chen, Xue-Qun Ren, Kai-Wu Xu, Hong Jing and Yu-Long He

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Oncotarget. 2015; 6:32193-32204. https://doi.org/10.18632/oncotarget.4975

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Abstract

Chang-Jiang Qin1,2, Xin-Ming Song1, Zhi-Hui Chen1, Xue-Qun Ren2, Kai-Wu Xu1, Hong Jing3 and Yu-Long He1

1 Department of Gastrointestinal and Pancreatic Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China

2 Department of Gastrointestinal Surgery, Huaihe Hospital of Hennan University, Kaifeng, China

3 Department of Pathology, Huaihe Hospital of Hennan University, Kaifeng, China

Correspondence to:

Xin-Ming Song, email:

Keywords: XRCC2, rectal cancer, preoperative radiotherapy, radioresistance

Received: April 21, 2015 Accepted: July 16, 2015 Published: July 22, 2015

Abstract

XRCC2 has been shown to increase the radioresistance of some cancers. Here, XRCC2 expression was investigated as a predictor of preoperative radiotherapy (PRT) treatment response in locally advanced rectal cancer (LARC). XRCC2 was found to be overexpressed in rectal cancer tissues resected from patients who underwent surgery without PRT. In addition, overall survival for LARC patients was improved in XRCC2-negative patients compared with XRCC2-positive patients after treatment with PRT (P < 0.001). XRCC2 expression was also associated with an increase in LARC radioresistance. Conversely, XRCC2-deficient cancer cells were more sensitive to irradiation in vitro, and a higher proportion of these cells underwent cell death induced by G2/M phase arrest and apoptosis. When XRCC2 was knocked down, the repair of DNA double-strand breaks caused by irradiation was impaired. Therefore, XRCC2 may increases LARC radioresistance by repairing DNA double-strand breaks and preventing cancer cell apoptosis. Moreover, the present data suggest that XRCC2 is a useful predictive biomarker of PRT treatment response in LARC patients. Thus, inhibition of XRCC2 expression or activity represents a potential therapeutic strategy for improving PRT response in LARC patients.


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