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Clinicopathological Significance of ZEB1 Protein in Patients with Hepatocellular Carcinoma
Zhou, Yan-Ming ; Zhou YM(周彦明) ; Cao, Lu ; Li, Bin ; Zhang, Rui-Xiu ; Sui, Cheng-Jun ; Yin, Zheng-Feng ; Yang, Jia-Mei
2012-05
关键词EPITHELIAL-MESENCHYMAL TRANSITION PROSTATE-CANCER CELLS TRANSCRIPTION FACTOR ZINC-FINGER CURATIVE RESECTION RISK-FACTORS METASTASIS EXPRESSION RECURRENCE DELTA-EF1
英文摘要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. 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. 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. This study shows that ZEB1 high expression was correlated with HCC malignant progression and subsequent poor patient survival by induction of EMT changes.; Foundation of Xiamen Science and Technology Bureau [3502Z20084010]; China National Key Projects for Infectious Disease [2008ZX10002-021]; National Natural Science Foundation of China [30772513]
语种英语
出版者SPRINGER
内容类型期刊论文
源URL[http://dx.doi.org/10.1245/s10434-011-1772-6]  
专题医学院-已发表论文
推荐引用方式
GB/T 7714
Zhou, Yan-Ming,Zhou YM,Cao, Lu,et al. Clinicopathological Significance of ZEB1 Protein in Patients with Hepatocellular Carcinoma[J],2012.
APA Zhou, Yan-Ming.,周彦明.,Cao, Lu.,Li, Bin.,Zhang, Rui-Xiu.,...&Yang, Jia-Mei.(2012).Clinicopathological Significance of ZEB1 Protein in Patients with Hepatocellular Carcinoma..
MLA Zhou, Yan-Ming,et al."Clinicopathological Significance of ZEB1 Protein in Patients with Hepatocellular Carcinoma".(2012).
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