No abstract

<p>PDF file - 55K, Expression fold-change of EMT-associated genes and microRNAs between the four compartments liver (L). liver invasion front (LIF). tumor invasion frot (TIF) and tumor center (Tc). All samples were normalized to 18s expression and fold change expression was calculated according to the 2-��ct method as described previously (15). P-Values (P) were assessed by using the Wilcoxon signed-rank test. (LIF vs. L: expression fold-change of target gene in liver invasion front compared to liver. LIF vs TIF: expression fold-change of target gene in liver invasion front compared to tumor invasion front. LIF vs Tc: expression fold-change of target gene in liver invasion front compared to tumor center. TIF vs L: expression fold-change of target gene in tumor invasion front compared to liver. TIF vs Tc: expression fold-change of target gene in tumor invasion front compared to tumor center. L vs Tc: expression fold-change of target gene in liver compared to tumor center).</p>

<p>PDF file - 38K</p>

<div>Abstract<p><b>Purpose:</b> Epithelial-to-mesenchymal transition (EMT) plays a pivotal role in tumor invasion and dissemination. EMT occurs predominantly at the tumor edge where it is induced by cytokines, the extracellular matrix environment, or hypoxia. In the tumor cell, it is further mediated by several transcription factors and microRNAs. The aim of this study was to explore the expression of EMT-associated genes at the invasive front in colorectal cancer and to evaluate their prognostic significance.</p><p><b>Experimental Design:</b> We evaluated the expression of 13 EMT-associated genes at the invasion front of 30 colorectal liver metastases by quantitative real-time PCR. Immunostaining against zinc finger E-box–binding homeobox 2 (ZEB2) was carried out on 175 primary colorectal cancer specimens and 30 colorectal liver metastases and correlated to clinical and histopathologic data. DLD-1 cells were transfected with siRNA and subjected to migration and invasion assays.</p><p><b>Results:</b> Gene expression analysis and immunohistochemistry showed an upregulation of ZEB2 at the invasion front in primary colorectal cancer and liver metastases. Overexpression of ZEB2 at the invasion front correlated significantly with tumor stage in primary colorectal cancer. Moreover, univariate and multivariate analysis revealed overexpression of ZEB2 at the invasion front as an independent prognostic marker for cancer-specific survival. Downregulation of ZEB2 by siRNA decreased the migration and invasion capacity of DLD-1 cells <i>in vitro</i>.</p><p><b>Conclusions:</b> Overexpression of ZEB2 at the invasion front correlates with tumor progression and predicts cancer-specific survival in primary colorectal cancer. Therefore, ZEB2 may be interesting as biomarker and potential target for treatment of colorectal cancer. <i>Clin Cancer Res; 17(24); 7654–63. ©2011 AACR</i>.</p></div>

<div>Abstract<p><b>Purpose:</b> Epithelial-to-mesenchymal transition (EMT) plays a pivotal role in tumor invasion and dissemination. EMT occurs predominantly at the tumor edge where it is induced by cytokines, the extracellular matrix environment, or hypoxia. In the tumor cell, it is further mediated by several transcription factors and microRNAs. The aim of this study was to explore the expression of EMT-associated genes at the invasive front in colorectal cancer and to evaluate their prognostic significance.</p><p><b>Experimental Design:</b> We evaluated the expression of 13 EMT-associated genes at the invasion front of 30 colorectal liver metastases by quantitative real-time PCR. Immunostaining against zinc finger E-box–binding homeobox 2 (ZEB2) was carried out on 175 primary colorectal cancer specimens and 30 colorectal liver metastases and correlated to clinical and histopathologic data. DLD-1 cells were transfected with siRNA and subjected to migration and invasion assays.</p><p><b>Results:</b> Gene expression analysis and immunohistochemistry showed an upregulation of ZEB2 at the invasion front in primary colorectal cancer and liver metastases. Overexpression of ZEB2 at the invasion front correlated significantly with tumor stage in primary colorectal cancer. Moreover, univariate and multivariate analysis revealed overexpression of ZEB2 at the invasion front as an independent prognostic marker for cancer-specific survival. Downregulation of ZEB2 by siRNA decreased the migration and invasion capacity of DLD-1 cells <i>in vitro</i>.</p><p><b>Conclusions:</b> Overexpression of ZEB2 at the invasion front correlates with tumor progression and predicts cancer-specific survival in primary colorectal cancer. Therefore, ZEB2 may be interesting as biomarker and potential target for treatment of colorectal cancer. <i>Clin Cancer Res; 17(24); 7654–63. ©2011 AACR</i>.</p></div>