Influence of Ku86 and XRCC4 expression in uterine cervical cancer on the response to preoperative radiotherapy
Influence of Ku86 and XRCC4 expression in uterine cervical cancer on the response to preoperative radiotherapy
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DOI：
10.1007/s00795-016-0136-5
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发表时间：
2016-02
影响因子：
1.8
通讯作者：
Y. Takada;M. Someya;Y. Matsumoto;M. Satoh;Kensei Nakata;M. Hori;Masato Saito;N. Hirokawa;K. Tateoka;Mizue Teramoto;Tsuyoshi Saito;T. Hasegawa;K. Sakata
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文献类型：
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作者：
Y. Takada;M. Someya;Y. Matsumoto;M. Satoh;Kensei Nakata;M. Hori;Masato Saito;N. Hirokawa;K. Tateoka;Mizue Teramoto;Tsuyoshi Saito;T. Hasegawa;K. Sakata
DNA双链断裂（DSB）是电离辐射引起的严重损伤。非同源末端连接（NHEJ）是修复DSB的主要机制。免疫组化分析参与NHEJ的蛋白质，如Ku86和XRCC4（X射线修复交叉互补蛋白4）可能有助于预测肿瘤的放射敏感性。我们研究了宫颈癌活检标本中DSB相关蛋白的表达与术前40戈伊病理效应之间的关系。2000年至2011年期间，119名宫颈癌患者接受了治疗。通过检查子宫切除标本，对术前放疗的病理效应进行分类。完全缓解（pCR）患者的5年总生存率显著高于无pCR患者（96.3% vs. 76.9%，P = 0.02）。Ku86和XRCC4低表达患者的pCR率显著高于其他患者（47.4vs.21.3%，P = 0.04）。Logistic回归分析显示Ku86和XRCC4低表达是pCR的显著预测因素（P = 0.03）。Ku86和XRCC4高表达患者的5年无转移率显著低于其他患者（79.3 vs. 93.5%，P = 0.02）。NHEJ相关蛋白可能影响宫颈癌的放射治疗效果。
DNA double-strand breaks (DSB) are severe damages induced by ionizing radiation. Non-homologous end joining (NHEJ) is a major mechanism for repairing DSB. Immunohistochemical analysis of proteins involved in NHEJ, such as Ku86 and XRCC4 (X-ray repair cross-complementing protein 4) may be useful for predicting tumor radiosensitivity. We examined the relationship between expression of DSB-related proteins in biopsy specimens of uterine cervical cancer and the pathological effect of 40 Gy of preoperative radiotherapy. 119 patients with uterine cervical cancer were treated between 2000 and 2011. Pathological effects of preoperative radiotherapy were classified by examining hysterectomy specimens. Patients with complete response (pCR) had a significantly better overall 5-year survival rate than those without pCR (96.3 vs. 76.9 %,P= 0.02). The pCR rate was significantly higher in patients with low Ku86 and XRCC4 expression than in other patients (47.4 vs. 21.3 %,P= 0.04). Logistic regression analysis also demonstrated that low Ku86 and XRCC4 expression was a significant predictor of pCR (P= 0.03). Patients with high Ku86 and XRCC4 expression had a significantly lower 5-year metastasis-free rate than others (79.3 vs. 93.5 %,P= 0.02). Proteins involved with NHEJ might have an influence on results of radiotherapy for uterine cervical cancer.