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作 者:严珊珊[1] 刘莉[1] 刘志刚[1] 曾木圣[1] 宋立兵[1] 夏云飞[1]
机构地区:[1]华南肿瘤学国家重点实验室
出 处:《癌症》2008年第9期979-983,共5页Chinese Journal of Cancer
基 金:国家自然科学基金(No.30570543;No.30070237);国家"863"计划项目(No.2006AA02Z4B4)~~
摘 要:背景与目的:DNA双链断裂(DNA double-strand break,DSB)是射线杀灭肿瘤细胞的主要机制,而同源重组(homologous recombination,HR)和非同源性末端连接(DNA nonhomologous end-joining,NHEJ)是DSB的两条重要修复途径。DNA-PK催化亚单位(catalytic subunit of DNA-dependent protein kinase,DNA-PKcs)是NHEJ途径的主要修复蛋白之一,在DSB中发挥着重要作用。本研究旨在通过检测鼻咽癌组织中DNA-PKcs的表达情况,探讨其与鼻咽癌临床病理特征及预后的关系。方法:采用免疫组化SP法检测223例鼻咽癌患者组织中DNA-PKcs的表达,并结合患者的临床及预后资料进行分析。结果:223例鼻咽癌患者中,DNA-PKcs的过表达率为36.8%。卡方检验显示,DNA-PKcs表达强弱与患者的性别、年龄、病理分型及N分期的相关性均无统计学意义(P>0.05),与TNM分期、T分期、M分期均有关(P<0.05)。单因素生存分析显示,DNA-PKcs过表达患者5年总生存率低于低表达患者(54.6%vs.79.4%),差异有统计学意义(P<0.05)。多因素Cox回归模型分析显示T、N、M分期及DNA-PKcs表达水平是影响鼻咽癌患者预后的独立因素(P<0.05)。结论:DNA-PKcs在大部分鼻咽癌组织中均有表达,DNA-PKcs的表达水平与鼻咽癌患者预后相关,对患者的预后判断有一定的指导意义。BACKGROUND & OBJECTIVE: DNA double-strand break (DSB) is the main mechanism of tumor cell death after irradiation. Homologous recombination (HR) and DNA nonhomologous end-joining (NHEJ) are two important ways to repair DSB. The catalytic subunit of DNA- dependent protein kinase (DNA-PKcs), an essential protein of NHEJ, plays a major role during DSB. This study was to investigate the expression of DNA-PKcs in nasopharyngeal carcinoma (NPC), and analyze its correlation to the clinicopathologic features and prognosis of NPC. METHODS: The expression of DNA-PKcs protein in 223 specimens of NPC tissues was detected by immunohistochemistry. The correlation of DNA-PKcs expression to clinicopathologic features and prognosis of NPC were analyzed. RESULTS: The overexpression rate of DNA-PKcs in 223 NPC specimens was 36.8%. The expression of DNA-PKcs had no significant correlations to gender, age, pathological type and N staging of NPC (P〉0.05), but had remarkable correlations to TNM, T and M staging (P〈0.05). The 5-year overall survival rate was significantly lower in the patients with overexpression of DNA-PKcs than in those with low expression of DNA-PKcs (54.6% vs. 79.4%, P〈0.05). T, N, M staging and the expression of DNA-PKcs were independent predictors for the overall survival of NPC (P 〈0.05). CONCLUSIONS. DNA-PKcs is positively expressed in the majority of NPC tissues. The expression level of DNA-PKcs is an important factor affecting the prognosis of NPC, which could be used as a prognostic predictor for NPC.
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