gms | German Medical Science

Introduction: 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 invasion front-specific expression of EMT-associated genes in colorectal cancer and to evaluate their prognostic significance.

Materials and methods: We evaluated the expression of 13 EMT-associated genes at the invasion front of 30 colorectal liver metastases by real-time-quantitative-PCR (qRT-PCR). Immunostaining against ZEB2 was performed on 117 primay colorectal cancer specimens and 30 colorectal liver metastases and correlated to clinical and histopathological data. DLD-1 cells were transfected with short interfering RNA (siRNA) and subjected to migration and invasion assays.

Results: Gene expression analysis and immunohistochemistry showed invasion front-specific upregulation of ZEB2 in primary colorectal cancer and liver metastases. Invasion front-specific overexpression of ZEB2 correlated significantly with tumor stage in primary colorectal cancer. Moreover, univariate and multivariate analysis revealed invasion front-specific overexpression of ZEB2 as an independent prognostic marker for cancer-specific overall survival. Downregulation of ZEB2 by siRNA decreased the migration and invasion capacity of DLD-1 cells in vitro.

Conclusion: Invasion front-specific overexpression of ZEB2 correlates with tumor progression and predicts cancer-specific overall survival in primary colorectal cancer. Therefore, ZEB2 may be interesting as biomarker and potential target for treatment of colorectal cancer.