Qin Chang-Jiang, Song Xin-Ming, Chen Zhi-Hui, Ren Xue-Qun, Xu Kai-Wu, Jing Hong, He Yu-Long
Department of Gastrointestinal and Pancreatic Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
Department of Gastrointestinal Surgery, Huaihe Hospital of Hennan University, Kaifeng, China.
Oncotarget. 2015 Oct 13;6(31):32193-204. doi: 10.18632/oncotarget.4975.
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.
已有研究表明，XRCC2可增强某些癌症的放射抗性。在此，对XRCC2表达作为局部晚期直肠癌（LARC）术前放疗（PRT）治疗反应预测指标进行了研究。发现未接受PRT手术患者切除的直肠癌组织中XRCC2过表达。此外，PRT治疗后，XRCC2阴性的LARC患者总生存率高于XRCC2阳性患者（P < 0.001）。XRCC2表达还与LARC放射抗性增加有关。相反，XRCC2缺陷的癌细胞在体外对辐射更敏感，且这些细胞中更高比例经历了由G2/M期阻滞和凋亡诱导的细胞死亡。当敲低XRCC2时，辐射引起的DNA双链断裂修复受损。因此，XRCC2可能通过修复DNA双链断裂和防止癌细胞凋亡来增加LARC的放射抗性。此外，目前的数据表明，XRCC2是LARC患者PRT治疗反应的有用预测生物标志物。因此，抑制XRCC2表达或活性代表了一种改善LARC患者PRT反应的潜在治疗策略。
