High expression of ZEB1 correlates with liver metastasis and poor prognosis in colorectal cancer

Zhang,Guang-Jun; Zhou,Tong; Tian,Hong-Peng; Liu,Zuo-Liang; Xia,Shu-Sen

doi:10.3892/ol.2012.1026

High expression of ZEB1 correlates with liver metastasis and poor prognosis in colorectal cancer

Authors:
- Guang-Jun Zhang
- Tong Zhou
- Hong-Peng Tian
- Zuo-Liang Liu
- Shu-Sen Xia
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Affiliations: The First Department of General Surgery, The Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan 637000, P.R. China
Published online on: November 14, 2012 https://doi.org/10.3892/ol.2012.1026
Pages: 564-568

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Abstract

Zinc finger E-box binding homeobox 1 (ZEB1) has been shown to promote invasion and metastasis in several types of human cancer and to have a prognostic role in certain cancers. However, the clinical significance of ZEB1 in colorectal cancer (CRC) has not been sufficiently investigated. This study aimed to address this issue. In this study, we compared the expression of ZEB1 between CRC tissues and normal adjacent mucosa using quantitative real-time RT-PCR. The association of ZEB1 expression with clinicopathological characteristics was analyzed by appropriate statistical analyses. Kaplan-Meier analysis and Cox proportional hazards regression models were used to investigate the association of ZEB1 expression with survival of patients. The results showed that the relative expression levels of ZEB1 were significantly higher in CRC tissues compared to the normal adjacent mucosa and higher expression of ZEB1 correlated with liver metastasis. Kaplan-Meier analysis indicated that patients with high ZEB1 had a poor overall survival. Moreover, the multivariate analysis showed that high expression of ZEB1 was an independent predictor of overall survival. Our data indicate the potential of ZEB1 as a novel prognostic biomarker for CRC.

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1.	Parkin DM, Bray F, Ferlay J and Pisani P: Global cancer statistics, 2002. CA Cancer J Clin. 55:74–108. 2005. View Article : Google Scholar
2.	Kobayashi H, Mochizuki H, Sugihara K, et al: Characteristics of recurrence and surveillance tools after curative resection for colorectal cancer: a multicenter study. Surgery. 141:67–75. 2007. View Article : Google Scholar : PubMed/NCBI
3.	Bates RC and Mercurio AM: The epithelial-mesenchymal transition (EMT) and colorectal cancer progression. Cancer Biol Ther. 4:365–370. 2005. View Article : Google Scholar : PubMed/NCBI
4.	Brabletz T, Hlubek F, Spaderna S, et al: Invasion and metastasis in colorectal cancer: epithelial-mesenchymal transition, mesenchymal-epithelial transition, stem cells and beta-catenin. Cells Tissues Organs. 179:56–65. 2005. View Article : Google Scholar : PubMed/NCBI
5.	Christiansen JJ and Rajasekaran AK: Reassessing epithelial to mesenchymal transition as a prerequisite for carcinoma invasion and metastasis. Cancer Res. 66:8319–8326. 2006. View Article : Google Scholar : PubMed/NCBI
6.	Klymkowsky MW and Savagner P: Epithelial-mesenchymal transition: A cancer researcher’s conceptual friend and foe. Am J Pathol. 174:1588–1593. 2009.PubMed/NCBI
7.	Spaderna S, Schmalhofer O, Hlubek F, et al: A transient, EMT-linked loss of basement membranes indicates metastasis and poor survival in colorectal cancer. Gastroenterology. 131:830–840. 2006. View Article : Google Scholar : PubMed/NCBI
8.	Eger A, Aigner K, Sonderegger S, et al: DeltaEF1 is a transcriptional repressor of E-cadherin and regulates epithelial plasticity in breast cancer cells. Oncogene. 24:2375–2385. 2005. View Article : Google Scholar : PubMed/NCBI
9.	Ohira T, Gemmill RM, Ferguson K, et al: WNT7a induces E-cadherin in lung cancer cells. Proc Natl Acad Sci U S A. 100:10429–10434. 2003. View Article : Google Scholar : PubMed/NCBI
10.	Chua HL, Bhat-Nakshatri P, Clare SE, et al: NF-kappaB represses E-cadherin expression and enhances epithelial to mesenchymal transit ion of mammary epithelial cells: Potential involvement of ZEB-1 and ZEB-2. Oncogene. 26:711–724. 2007. View Article : Google Scholar
11.	Graham TR, Zhau HE, Odero-Marah VA, et al: Insulin-like growth factor-I-dependent up-regulation of ZEB1 drives epithelial-to-mesenchymal transition in human prostate cancer cells. Cancer Res. 68:2479–2488. 2008. View Article : Google Scholar : PubMed/NCBI
12.	Spaderna S, Schmalhofer O, Wahlbuhl M, et al: The transcriptional repressor ZEB1 promotes metastasis and loss of cell polarity in cancer. Cancer Res. 68:537–44. 2008. View Article : Google Scholar : PubMed/NCBI
13.	Sánchez-Tilló E, Lázaro A, Torrent R, et al: ZEB1 represses E-cadherin and induces an EMT by recruiting the SWI/SNF chromatin-remodeling protein BRG1. Oncogene. 29:3490–3500. 2010.PubMed/NCBI
14.	Xiong H, Hong J, Du W, et al: Roles of STAT3 and ZEB1 proteins in E-cadherin down-regulation and human colorectal cancer epithelial-mesenchymal transition. J Biol Chem. 287:5819–5832. 2012. View Article : Google Scholar : PubMed/NCBI
15.	Waldmann J, Feldmann G, Slater EP, et al: Expression of the zinc-finger transcription factor Snail in adrenocortical carcinoma is associated with decreased survival. Br J Cancer. 99:1900–1907. 2008. View Article : Google Scholar : PubMed/NCBI
16.	Iwatsuki M, Mimori K, Yokobori T, et al: Epithelial-mesenchymal transition in cancer development and its clinical significance. Cancer Sci. 101:293–299. 2010. View Article : Google Scholar : PubMed/NCBI
17.	Drake JM, Strohbehn G, Bair TB, et al: ZEB1 enhances transendothelial migration and represses the epithelial phenotype of prostate cancer cells. Mol Biol Cell. 20:2207–2217. 2009. View Article : Google Scholar : PubMed/NCBI
18.	Takeyama Y, Sato M, Horio M, et al: Knockdown of ZEB1, a master epithelial-to-mesenchymal transition (EMT) gene, suppresses anchorage-independent cell growth of lung cancer cells. Cancer Lett. 296:216–224. 2010. View Article : Google Scholar : PubMed/NCBI
19.	Singh M, Spoelstra NS, Jean A, et al: ZEB1 expression in type I vs type II endometrial cancers: a marker of aggressive disease. Mod Pathol. 21:912–923. 2008. View Article : Google Scholar : PubMed/NCBI
20.	Okugawa Y, Toiyama Y, Tanaka K, et al: Clinical significance of zinc finger E-box binding homeobox 1 (ZEB1) in human gastric cancer. J Surg Oncol. 106:280–285. 2011. View Article : Google Scholar : PubMed/NCBI
21.	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. View Article : Google Scholar : PubMed/NCBI
22.	Shen A, Zhang Y, Yang H, et al: Overexpression of ZEB1 relates to metastasis and invasion in osteosarcoma. J Surg Oncol. 105:830–834. 2012. View Article : Google Scholar : PubMed/NCBI
23.	Stridh P, Thessen Hedreul M, Beyeen AD, et al: Fine-mapping resolves Eae23 into two QTLs and implicates ZEB1 as a candidate gene regulating experimental neuroinflammation in rat. PLoS One. 5:e127162010. View Article : Google Scholar : PubMed/NCBI
24.	Hidaka T, Nakahata S, Hatakeyama K, et al: Down-regulation of TCF8 is involved in the leukemogenesis of adult T-cell leukemia/lymphoma. Blood. 112:383–393. 2008. View Article : Google Scholar : PubMed/NCBI
25.	Genetta T, Ruezinsky D and Kadesch T: Displacement of an E-box-binding repressor by basic helix-loop-helix proteins: Implications for B-cell specificity of the immunoglobulin heavy-chain enhancer. Mol Cell Biol. 14:6153–6163. 1994. View Article : Google Scholar : PubMed/NCBI
26.	Fontemaggi G, Gurtner A, Strano S, et al: The transcriptional repressor ZEB regulates p73 expression at the crossroad between proliferation and differentiation. Mol Cell Biol. 21:8461–8470. 2001. View Article : Google Scholar : PubMed/NCBI
27.	Putzke AP, Ventura AP, Bailey AM, et al: Metastatic progression of prostate cancer and e-cadherin regulation by zeb1 and SRC family kinases. Am J Pathol. 179:400–410. 2011. View Article : Google Scholar : PubMed/NCBI
28.	Argast GM, Krueger JS, Thomson S, et al: Inducible expression of TGFbeta, Snail and Zeb1 recapitulates EMT in vitro and in vivo in a NSCLC model. Clin Exp Metastasis. 28:593–614. 2011. View Article : Google Scholar : PubMed/NCBI
29.	Roy BC, Kohno T, Iwakawa R, et al: Involvement of LKB1 in epithelial-mesenchymal transition (EMT) of human lung cancer cells. Lung Cancer. 70:136–145. 2010. View Article : Google Scholar : PubMed/NCBI
30.	Kim T, Veronese A, Pichiorri F, et al: p53 regulates epithelialmesenchymal transition through microRNAs targeting ZEB1 and ZEB2. J Exp Med. 208:875–883. 2011. View Article : Google Scholar : PubMed/NCBI