title: Clinicopathological significance of ZEB1 protein in patients with hepatocellular carcinoma.
abstract: BACKGROUND
  ZEB1, a member of the ZFH family of proteins (zinc-finger E-box binding homeobox), plays a central role in epithelial-mesenchymal transition (EMT) during carcinogenesis. In this study, we investigated the expression of ZEB1 in patients with hepatocellular carcinoma (HCC) and its clinical effects with underlying mechanisms.
  
  
  METHODS
  Expression levels of ZEB1 were assessed by Western blot in 5 HCC cell lines and in paired cancerous and noncancerous tissues from 110 patients with HCC. Short-hairpin RNA (shRNA) interference for ZEB1 was performed in MHCC-97H cell line.
  
  
  RESULTS
  ZEB1 protein was detected at a relatively high level in metastatic human HCC cell lines (MHCC-97L and MHCC-97H) when compared with that in nonmetastatic HCC cell lines (Hep3B, PLC and Huh-7). ZEB1 was expressed at high levels in 72 of 110 HCC patients (65.4%) and correlated with advanced TNM stage, tumor size >5 cm, intrahepatic metastasis, vascular invasion, and frequent early recurrence. The results of multivariate analysis revealed that ZEB1 high expression was a significant prognostic factor for poor overall and disease-free survivals. Silencing ZEB1 resulted in significant suppression of motility of MHCC-97H cell line, which was accompanied with increased expression of the epithelial marker E-cadherin and decreased expression of the mesenchymal markers N-cadherin and vimentin. Furthermore, silencing ZEB1 prevented the spread of intrahepatic metastasis and increased overall survival in mouse orthotopic tumor models.
  
  
  CONCLUSIONS
  This study shows that ZEB1 high expression was correlated with HCC malignant progression and subsequent poor patient survival by induction of EMT changes.
authors.affiliation: Department of Hepato-Biliary-Pancreato-Vascular Surgery, First Affiliated Hospital of Xiamen University, Xiamen, China.
authors.forename: Yan-Ming
authors.initials: YM
authors.lastname: Zhou
authors.forename: Lu
authors.initials: L
authors.lastname: Cao
authors.forename: Bin
authors.initials: B
authors.lastname: Li
authors.forename: Rui-Xiu
authors.initials: RX
authors.lastname: Zhang
authors.forename: Cheng-Jun
authors.initials: CJ
authors.lastname: Sui
authors.forename: Zheng-Feng
authors.initials: ZF
authors.lastname: Yin
authors.forename: Jia-Mei
authors.initials: JM
authors.lastname: Yang
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015820:Cadherins / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology* / Q000556:secondary; D002465:Cell Movement / Q000502:physiology; D002471:Cell Transformation, Neoplastic / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D018450:Disease Progression; D018572:Disease-Free Survival; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D005260:Female; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D009367:Neoplasm Staging; D014157:Transcription Factors / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014746:Vimentin / Q000378:metabolism; D000071799:Zinc Finger E-box-Binding Homeobox 1
chemical_list: D014408:Biomarkers, Tumor; D015820:Cadherins; D018398:Homeodomain Proteins; D014157:Transcription Factors; D014746:Vimentin; C486307:ZEB1 protein, human; D000071799:Zinc Finger E-box-Binding Homeobox 1