title: Overexpression of Hippo pathway effector TAZ in tongue squamous cell carcinoma: correlation with clinicopathological features and patients' prognosis.
abstract: BACKGROUND
  Transcriptional coactivator with PDZ-binding motif (TAZ) is a key downstream effector of Hippo signaling pathway involved in stem cell differentiation and organ development. Recently, its deregulation has been linked to initiation and progression of various cancers. The purpose of this study was to investigate the expression of TAZ in tongue squamous cell carcinoma (TSCC) and its prognostic value in predicting patients' outcomes.
  
  
  METHODS
  TAZ expression and localization in a panel of TSCC cell lines and human immortalized oral epithelial cell (HIOEC) were determined by real-time RT-PCR, western blotting, and immunofluorescence. In 52 TSCC tumor specimens with detailed clinical and follow-up data, TAZ abundance was examined by immunohistochemistry and its associations with clinicopathological parameters, Ki-67 expression and patients' survival were further assessed.
  
  
  RESULTS
  TAZ mRNA and protein levels were significantly higher in TSCC cells and specimens than those in non-cancerous cells and normal tongue mucosa. Overexpression of TAZ in TSCC was significantly associated with tumor size (P = 0.033), pathological grade (P = 0.026), clinical stage (P = 0.013), Ki-67 expression (P = 0.0485), and reduced overall and disease-free survival (Kaplan-Meier analysis, log-rank test, P = 0.020, 0.019, respectively). Multivariate Cox regression analysis identified TAZ as an important independent predictor for survival of patients with TSCC [HR (hazard ratio), 4.351; 95% CI (95% confidence interval), 1.477-12.819; P = 0.008].
  
  
  CONCLUSIONS
  Our data indicate that aberrant TAZ overexpression is associated with key clinicopathological features and poor survival in TSCC. These results suggest that TAZ might play critical roles in tumorigenesis of TSCC and become a novel prognostic biomarker and potential therapeutic target for this malignancy.
authors.affiliation: Institute of Stomatology, Nanjing Medical University, Nanjing, China; Department of oral and maxillofacial surgery, Affiliated Stomatological Hospital, Nanjing Medical University, Nanjing, China.
authors.forename: Zicheng
authors.initials: Z
authors.lastname: Wei
authors.forename: Yanling
authors.initials: Y
authors.lastname: Wang
authors.forename: Zhongwu
authors.initials: Z
authors.lastname: Li
authors.forename: Chunping
authors.initials: C
authors.lastname: Yuan
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Dongmiao
authors.initials: D
authors.lastname: Wang
authors.forename: Jinhai
authors.initials: J
authors.lastname: Ye
authors.forename: Hongbin
authors.initials: H
authors.lastname: Jiang
authors.forename: Yunong
authors.initials: Y
authors.lastname: Wu
authors.forename: Jie
authors.initials: J
authors.lastname: Cheng
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis; D002294:Carcinoma, Squamous Cell / Q000737:chemistry* / Q000473:pathology / Q000556:secondary; D018929:Cell Culture Techniques; D002460:Cell Line; D045744:Cell Line, Tumor; D018572:Disease-Free Survival; D004847:Epithelial Cells / Q000166:cytology; D005260:Female; D005500:Follow-Up Studies; D005544:Forecasting; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000032:analysis*; D019394:Ki-67 Antigen / Q000032:analysis; D008197:Lymph Node Excision; D008207:Lymphatic Metastasis / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009061:Mouth Mucosa / Q000166:cytology; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011379:Prognosis; D015996:Survival Rate; D014062:Tongue Neoplasms / Q000737:chemistry* / Q000473:pathology; D015534:Trans-Activators; D014157:Transcription Factors; D000091364:Transcriptional Coactivator with PDZ-Binding Motif Proteins; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D047908:Intracellular Signaling Peptides and Proteins; D019394:Ki-67 Antigen; D015534:Trans-Activators; D014157:Transcription Factors; D000091364:Transcriptional Coactivator with PDZ-Binding Motif Proteins; C551991:WWTR1 protein, human
keywords: Hippo signaling; TAZ; prognostic marker; tongue squamous cell carcinoma