title: Enhancer of zeste homolog 2 overexpression in nasopharyngeal carcinoma: an independent poor prognosticator that enhances cell growth.
abstract: OBJECTIVE
  As a key component of polycomb-repressive complex 2, enhancer of zeste homolog 2 (EZH2) represses target genes through histone methylation and is frequently overexpressed and associated with poor prognosis in common carcinomas. For the first time, we reported EZH2 expression and its biological and clinical significance in nasopharyngeal carcinoma (NPC).
  
  
  METHODS
  In NPC cell lines and specimens, endogenous expression of EZH2 mRNA and protein was determined by semiquantitative reverse transcription-polymerase chain reaction and immunoblotting, respectively. To analyze the effect on cell growth, stable silencing of EZH2 was established in EZH2-expressing TW02 NPC cells with RNA interference. EZH2 immunolabeling was assessable for 89 primary NPC biopsy samples and correlated with clinicopathological variables, disease-specific survival (DSS), and overall survival (OS).
  
  
  RESULTS
  Growth activity of TW02 cells was significantly suppressed (p < 0.001) with stable EZH2 silencing. Compared with normal nasopharyngeal tissue, expression levels of EZH2 transcript and protein were apparently upregulated in NPC specimens. As a continuous variable, higher EZH2 expression preferentially occurred in NPCs of T3 to T4 stages (p = 0.03) and significantly predicted inferior DSS (p = 0.0010) and OS (p = 0.004). The prognostic implications for DSS (p = 0.010) and OS (p = 0.006) still remained valid when using the median (≥ 60%) of EZH2 immunolabeling index to dichotomize the cohort. In the multivariate model, higher EZH2 expression was an independent adverse factor of both DSS (p = 0.012) and OS (p = 0.011), along with American Joint Committee on Cancer Stages III to IV (p = 0.024 for DSS, p = 0.017 for OS).
  
  
  CONCLUSIONS
  At least partly through promoting cell growth, EZH2 implicates disease progression, confers tumor aggressiveness, and represents an independent adverse prognosticator in patients with NPC.
authors.affiliation: Department of Otolaryngology, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Chung-Feng
authors.initials: CF
authors.lastname: Hwang
authors.forename: Hsuan-Ying
authors.initials: HY
authors.lastname: Huang
authors.forename: Chang-Han
authors.initials: CH
authors.lastname: Chen
authors.forename: Chih-Yen
authors.initials: CY
authors.lastname: Chien
authors.forename: Yao-Chung
authors.initials: YC
authors.lastname: Hsu
authors.forename: Chien-Feng
authors.initials: CF
authors.lastname: Li
authors.forename: Fu-Min
authors.initials: FM
authors.lastname: Fang
mesh_terms: D000328:Adult; D000368:Aged; D002277:Carcinoma; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D018450:Disease Progression; D000071221:Enhancer of Zeste Homolog 2 Protein; D005260:Female; D020868:Gene Silencing; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D009305:Nasopharynx / Q000378:metabolism; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009367:Neoplasm Staging; D063151:Polycomb Repressive Complex 2; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D063151:Polycomb Repressive Complex 2