Up-Regulation of Enhancer of Zeste Homolog 2 Is Associated Positively With Cyclin Dl Overexpression and Poor Clinical Outcome in Head and Neck Squamous Cell Carcinoma

摘要

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 Dl 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 Dl expression (P = .O34) 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 Dl 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 diseasefree 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 Dl can serve as a more powerful prognostic predictor for patients with HNSCC.