Enhancer of zeste homolog 2 is a novel prognostic biomarker in nonsmall cell lung cancer

BACKGROUND: Enhancer of zeste homolog 2 (EZH2) epigenetically silences many genes through the trimethylation of histone H3 lysine 27 and is implicated in tumor growth, invasion, and metastasis. However, its role in lung cancer has not been well characterized. The objective of the current study was to elucidate the role of EZH2 in nonsmall cell lung cancer (NSCLC) by investigating both clinical samples and cell lines. METHODS: An immunohistochemical analysis of EZH2 expression was performed in samples from patients with stage I NSCLC to investigate the association of EZH2 expression levels with clinicopathologic variables. An in vitro cell growth assay and a Matrigel invasion assay also were conducted in the EZH2-expressing NSCLC cell lines A549 and H1299 after knocking down EZH2 expression by using an EZH2-specific short-hairpin RNA. RESULTS: The immunohistochemical analysis classified stage I NSCLC samples (n 106) into a negative EZH2 expression group (n 40; 37.7%) and a positive EZH2 expression group (n 66; 62.3%). Positive EZH2 expression was associated significantly with larger tumor size (P.014). Kaplan-Meier survival analyses and log-rank tests demonstrated that patients whose samples were classified into the positive EZH2 expression group had a significantly shorter overall survival (P.015). Experiments in the NSCLC cell lines revealed that the knockdown of EZH2 expression reduced the tumor growth rate and invasive activity. CONCLUSIONS: The current results indicated that EZH2 promotes progression and invasion of NSCLC, and its expression is a novel prognostic biomarker in NSCLC. Cancer 2012; 118: 1599-606. VC 2011 American Cancer Society.