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.
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.
Authors: Erick Riquelme; Milind Suraokar; Carmen Behrens; Heather Y Lin; Luc Girard; Monique B Nilsson; George Simon; Jing Wang; Kevin R Coombes; J Jack Lee; Waun Ki Hong; John Heymach; John D Minna; Ignacio I Wistuba Journal: Clin Cancer Res Date: 2014-05-21 Impact factor: 12.531
Authors: Lauren Krill; Wei Deng; Ramez Eskander; David Mutch; Susan Zweizig; Bang Hoang; Olga Ioffe; Leslie Randall; Heather Lankes; David S Miller; Michael Birrer Journal: Gynecol Oncol Date: 2019-12-13 Impact factor: 5.482
Authors: Ana I Robles; Eri Arai; Ewy A Mathé; Hirokazu Okayama; Aaron J Schetter; Derek Brown; David Petersen; Elise D Bowman; Rintaro Noro; Judith A Welsh; Daniel C Edelman; Holly S Stevenson; Yonghong Wang; Naoto Tsuchiya; Takashi Kohno; Vidar Skaug; Steen Mollerup; Aage Haugen; Paul S Meltzer; Jun Yokota; Yae Kanai; Curtis C Harris Journal: J Thorac Oncol Date: 2015-07 Impact factor: 15.609
Authors: Carmen Behrens; Luisa M Solis; Heather Lin; Ping Yuan; Ximing Tang; Humam Kadara; Erick Riquelme; Hector Galindo; Cesar A Moran; Neda Kalhor; Stephen G Swisher; George R Simon; David J Stewart; J Jack Lee; Ignacio I Wistuba Journal: Clin Cancer Res Date: 2013-10-04 Impact factor: 12.531