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Clinicopathological Significance of ZEB1 Protein in Patients with Hepatocellular Carcinoma

  • Translational Research and Biomarkers
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

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.

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Acknowledgment

Supported by Foundation of Xiamen Science and Technology Bureau (3502Z20084010), China National Key Projects for Infectious Disease (2008ZX10002-021) and the National Natural Science Foundation of China (30772513).

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Authors and Affiliations

  1. Department of Hepato-Biliary-Pancreato-Vascular Surgery, First Affiliated Hospital of Xiamen University, Xiamen, China

    Yan-Ming Zhou MD & Bin Li MS

  2. Department of Special Treatment, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China

    Yan-Ming Zhou MD, Cheng-Jun Sui MD & Jia-Mei Yang MS

  3. Department of Molecular Oncology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China

    Lu Cao MS, Rui-Xiu Zhang MS & Zheng-Feng Yin PhD

Authors
  1. Yan-Ming Zhou MD
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  2. Lu Cao MS
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  3. Bin Li MS
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  4. Rui-Xiu Zhang MS
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  5. Cheng-Jun Sui MD
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  6. Zheng-Feng Yin PhD
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  7. Jia-Mei Yang MS
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Corresponding author

Correspondence to Zheng-Feng Yin PhD.

Additional information

Yan-Ming Zhou and Lu Cao contributed equally to this study.

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Zhou, YM., Cao, L., Li, B. et al. Clinicopathological Significance of ZEB1 Protein in Patients with Hepatocellular Carcinoma. Ann Surg Oncol 19, 1700–1706 (2012). https://doi.org/10.1245/s10434-011-1772-6

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  • DOI: https://doi.org/10.1245/s10434-011-1772-6

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