BRCC3 acts as a prognostic marker in nasopharyngeal carcinoma patients treated with radiotherapy and mediates radiation resistance in vitro.
BRCC3 acts as a prognostic marker in nasopharyngeal carcinoma patients treated with radiotherapy and mediates radiation resistance in vitro.
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BRCC3作为接受放疗的鼻咽癌患者的预后标志物并介导体外放射抵抗
DOI：
10.1186/s13014-015-0427-3
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发表时间：
2015-05-30
期刊：
影响因子：
--
通讯作者：
Xia Y
中科院分区：
文献类型：
--
作者：
Tu Z;Xu B;Qu C;Tao Y;Chen C;Hua W;Feng G;Chang H;Liu Z;Li G;Jiang C;Yi W;Zeng M;Xia Y
背景brcc3在乳腺肿瘤中异常表达，参与DNA损伤反应。BRCC3对鼻咽癌预后和放射敏感性的影响尚不清楚。方法对100例鼻咽癌组织进行BRCC3的免疫组化分析，发现BRCC3蛋白水平与患者生存期相关。采用Western-blotting和real-time PCR检测鼻咽癌细胞系BRCC3的表达。此外，我们还评估了BRCC3基因敲低对照射后鼻咽癌细胞克隆存活、DNA损伤修复和细胞周期分布的影响。结果BRCC3蛋白水平与鼻咽癌患者总生存率（P< 0.001）和3年局部-区域无复发生存率（P= 0.034）呈负相关。多因素分析显示BRCC3表达是独立的预后因素（P= 0.010）。BRCC3在鼻咽癌放射耐药细胞中的表达明显高于放射敏感细胞。BRCC3的敲低增加了细胞存活率，减弱了DNA损伤修复，导致辐射耐药鼻咽癌细胞的G2/M细胞周期阻滞。结论BRCC3在鼻咽癌患者中高表达与低生存率相关。BRCC3基因敲低可减轻鼻咽癌细胞的放射耐药。这些发现提示BRCC3作为鼻咽癌预后生物标志物和新靶点的实用性。
BackgroundBRCC3 has been found to be aberrantly expressed in breast tumors and involved in DNA damage response. The contribution of BRCC3 to nasopharyngeal carcinoma prognosis and radiosensitivity is still unclear.MethodsImmunohistochemical analysis of BRCC3 was carried out in 100 nasopharyngeal carcinoma tissues, and the protein level was correlated to patient survival. BRCC3 expression of nasopharyngeal carcinoma cell lines was determined by Western-blotting and real-time PCR. Additionally, the effects of BRCC3 knockdown on nasopharyngeal carcinoma cell clongenic survival, DNA damage repair, and cell cycle distribution after irradiation was assessed.ResultsThe BRCC3 protein level was inversely correlated with nasopharyngeal carcinoma patient overall survival (P< 0.001) and 3-year loco-regional relapse-free survival (P= 0.034). Multivariate analysis demonstrated that BRCC3 expression was an independent prognostic factor (P= 0.010). The expression of BRCC3 was much higher in radioresistant nasopharyngeal carcinoma cells than in radiosensitive cells. Knockdown of BRCC3 increased the cell survival fraction, attenuated DNA damage repair and resulted in G2/M cell cycle arrest in radioresistant NPC cells.ConclusionsHigh BRCC3 expression in nasopharyngeal carcinoma patients is associated with poor survival. BRCC3 knockdown could abate the radioresistance in nasopharyngeal carcinoma cells. These findings suggest the utility of BRCC3 as a prognostic biomarker and novel target for nasopharyngeal carcinoma.