title: EZH2 is associated with poor prognosis in head-and-neck squamous cell carcinoma via regulating the epithelial-to-mesenchymal transition and chemosensitivity.
abstract: OBJECTIVE
  Increasing evidence suggests that epigenetic regulation is responsible for tumor initiation and progression in head and neck squamous cell carcinoma (HNSCC). Although the polycomb group protein enhancer zeste homolog 2 (EZH2) is upregulated and a key epigenetic modifier implicated in various cancers, its molecular mechanism in HNSCC remains unknown. Herein, we investigated the role of EZH2 in HNSCC progression and its clinical implication as an HNSCC risk predictor.
  
  
  METHODS
  A retrospective analysis was performed on 90 HNSCC patients who had curative surgery between 1999 and 2011. Patients with high and low EZH2 expression were compared by the various clinicopathological factors. Survival rates were estimated by the Kaplan-Meier method and log-rank test was used to determine significance. For functional in vitro analysis, migration/invasion assay and Western blotting were performed after EZH2 knockdown using siRNA. In addition, cell proliferation was measured to clarify the role of EZH2 on cisplatin chemotherapy.
  
  
  RESULTS
  In patients with HNSCC, high EZH2 expression was correlated with advanced T stage and poor survival outcome. RNAi analysis revealed that EZH2 silencing increased E-cadherin expression while decreasing that of N-cadherin and Vimentin without altering Snail/Slug signaling, which led to decreased cell migration/invasion. EZH2 is also associated with tumor aggressiveness via regulating the epithelial-to-mesenchymal transition. Furthermore, we show that high EZH2 expression decreases sensitivity to cisplatin-based chemotherapy.
  
  
  CONCLUSIONS
  Our results indicate that EZH2 may not be only a predictive and prognostic biomarker but also a potential personalized therapeutic target for the treatment of HNSCC.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Research Institute for Medical Science, Chungnam National University College of Medicine, Daejeon, Republic of Korea.
authors.forename: Jae Won
authors.initials: JW
authors.lastname: Chang
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Research Institute for Medical Science, Chungnam National University College of Medicine, Daejeon, Republic of Korea.
authors.forename: Seo Young
authors.initials: SY
authors.lastname: Gwak
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Research Institute for Medical Science, Chungnam National University College of Medicine, Daejeon, Republic of Korea.
authors.forename: Geun-Ae
authors.initials: GA
authors.lastname: Shim
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Research Institute for Medical Science, Chungnam National University College of Medicine, Daejeon, Republic of Korea.
authors.forename: Lihua
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, Research Institute of Medical Science, Konkuk University School of Medicine, Seoul, Republic of Korea.
authors.forename: Young Chang
authors.initials: YC
authors.lastname: Lim
authors.affiliation: Research Institute for Medical Sciences and Pathology, Chungnam National University College of Medicine, Daejeon, Republic of Korea.
authors.forename: Jin Man
authors.initials: JM
authors.lastname: Kim
authors.affiliation: Research Institute for Medical Sciences and Pathology, Chungnam National University College of Medicine, Daejeon, Republic of Korea.
authors.forename: Min Gyu
authors.initials: MG
authors.lastname: Jung
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Research Institute for Medical Science, Chungnam National University College of Medicine, Daejeon, Republic of Korea. Electronic address: bskoo515@cnuh.co.kr.
authors.forename: Bon Seok
authors.initials: BS
authors.lastname: Koo
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D015820:Cadherins / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000628:therapy; D002945:Cisplatin / Q000627:therapeutic use; D000071221:Enhancer of Zeste Homolog 2 Protein; D044127:Epigenesis, Genetic; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D005260:Female; D006258:Head and Neck Neoplasms / Q000378:metabolism* / Q000628:therapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D063151:Polycomb Repressive Complex 2 / Q000378:metabolism*; D011379:Prognosis; D034741:RNA, Small Interfering; D012189:Retrospective Studies; D016019:Survival Analysis; D014746:Vimentin / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D015820:Cadherins; D034741:RNA, Small Interfering; D014746:Vimentin; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D063151:Polycomb Repressive Complex 2; D002945:Cisplatin
keywords: Chemosensitivity; Enhancer zeste homolog 2 (EZH2); Epithelial-to-mesenchymal transition (EMT); Head-and-neck squamous cell carcinoma (HNSCC); Prognosis