Up-regulation of enhancer of zeste homolog 2 is associated positively with cyclin D1 overexpression and poor clinical outcome in head and neck squamous cell carcinoma
Up-regulation of enhancer of zeste homolog 2 is associated positively with cyclin D1 overexpression and poor clinical outcome in head and neck squamous cell carcinoma
复制标题
Zeste 同源物 2 增强子的上调与头颈鳞状细胞癌中 Cyclin D1 过表达和不良临床结果呈正相关
DOI：
10.1002/cncr.26575
复制
发表时间：
2012-06-01
期刊：
影响因子：
6.2
通讯作者：
Chen, Wantao
中科院分区：
文献类型：
--
作者：
Cao, Wei;Feng, Zhien;Chen, Wantao
背景：作者先前观察到zeste同源物增强子2 （EZH2）过表达与口腔癌的发展显著相关。在目前的研究中，他们调查了EZH2是否可以作为头颈部鳞状细胞癌（HNSCC）患者的预后预测因子。方法：采用逆转录聚合酶链反应（PCR）和Western blot方法检测EZH2在HNSCC细胞中的表达水平。此外，通过小干扰RNA （small interfering RNA, siRNA）介导的敲低，研究EZH2消融对HNSCC细胞增殖和侵袭的影响。采用Real-time PCR和免疫组化技术检测46例HNSCC样本中EZH2和cyclin D1的表达，并对124例独立样本进行免疫组化检测。结果：EZH2在HNSCC标本和细胞系中的表达显著升高。EZH2沉默后，HNSCC细胞的增殖和侵袭明显受到抑制。EZH2表达与cyclin D1表达（P = 0.034）和肿瘤分化（P = 0.020）密切相关。此外，EZH2信使RNA水平和EZH2蛋白水平与组织学严重程度的迹象密切相关（P = 0.012和P = 0.032）。单因素分析显示，EZH2高表达与较差的总生存期（P = 0.001）和无病生存期（P = 0.002）相关。联合表达EZH2和cyclin D1对HNSCC患者的预后能力优于单独表达任何一种标志物。在多变量分析中，EZH2表达被确定为总体生存和无病生存的独立预测因子。结论：目前的研究结果表明，EZH2是HNSCC患者的独立预后指标。此外，分析EZH2和cyclin D1的联合表达可以作为HNSCC患者更有效的预后预测因子。2011年癌症。(c) 2011年美国癌症协会。
BACKGROUND: The authors previously observed that enhancer of zeste homolog 2 (EZH2) overexpression was associated significantly with the development of oral cancer. In the current study, they investigated whether EZH2 can function as a prognostic predictor for patients with head and neck squamous cell carcinoma (HNSCC). METHODS: Expression levels of EZH2 in HNSCC cells were detected using reverse transcriptase-polymerase chain reaction (PCR) and Western blot analyses. In addition, the effects of EZH2 ablation on the proliferation and invasion of HNSCC cells were investigated through small interfering RNA (siRNA)-mediated knockdown. Real-time PCR and immunohistochemistry were used to evaluate EZH2 and cyclin D1 expression in 46 HNSCC samples, and the expression levels also were re-evaluated in 124 independent samples by immunohistochemistry. RESULTS: EZH2 expression was elevated remarkably in HNSCC specimens and cell lines. Upon EZH2 silencing, the proliferation and invasion of HNSCC cells were remarkably suppressed. EZH2 expression frequently was correlated with cyclin D1 expression (P = .034) and tumor differentiation (P = .020). In addition, both EZH2 messenger RNA levels and EZH2 protein levels were strongly associated with signs of histologic severity (P = .012 and P = .032, respectively). Univariate analysis revealed that high EZH2 expression was associated with worse overall survival (P = .001) and disease-free survival (P = .002). The combined expression of EZH2 and cyclin D1 had superior prognostic ability for patients with HNSCC than the expression of either marker alone. In multivariate analysis, EZH2 expression was identified as an independent predictor of overall and disease-free survival. CONCLUSIONS: The current results indicated that EZH2 is an independent prognostic indicator for patients with HNSCC. In addition, an analysis of the combined expression of EZH2 and cyclin D1 can serve as a more powerful prognostic predictor for patients with HNSCC. Cancer 2011. (c) 2011 American Cancer Society.