title: Overexpression of ZEB2 at the invasion front of colorectal cancer is an independent prognostic marker and regulates tumor invasion in vitro.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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 in vitro.
  
  
  CONCLUSIONS
  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.
authors: Department of General, Visceral and Transplantation Surgery, Institute of Pathology, University of Heidelberg, and German Cancer Research Center, Division of Biostatistics, Heidelberg, Germany. christoph.kahlert@med.uni-heidelberg.de
authors: Christoph
authors: C
authors: Kahlert
authors: Saleh
authors: S
authors: Lahes
authors: Praveen
authors: P
authors: Radhakrishnan
authors: Shamik
authors: S
authors: Dutta
authors: Carolin
authors: C
authors: Mogler
authors: Esther
authors: E
authors: Herpel
authors: Karsten
authors: K
authors: Brand
authors: Gunnar
authors: G
authors: Steinert
authors: Martin
authors: M
authors: Schneider
authors: Martin
authors: M
authors: Mollenhauer
authors: Christoph
authors: C
authors: Reissfelder
authors: Fee
authors: F
authors: Klupp
authors: Johannes
authors: J
authors: Fritzmann
authors: Christina
authors: C
authors: Wunder
authors: Axel
authors: A
authors: Benner
authors: Matthias
authors: M
authors: Kloor
authors: Cathrin
authors: C
authors: Huth
authors: Pietro
authors: P
authors: Contin
authors: Alexis
authors: A
authors: Ulrich
authors: Moritz
authors: M
authors: Koch
authors: Jürgen
authors: J
authors: Weitz
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000556:secondary; D008297:Male; D035683:MicroRNAs / Q000235:genetics; D008875:Middle Aged; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness; D011379:Prognosis; D034622:RNA Interference; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000074165:Zinc Finger E-box Binding Homeobox 2
chemical_list: D014408:Biomarkers, Tumor; D018398:Homeodomain Proteins; D035683:MicroRNAs; D012097:Repressor Proteins; C492363:ZEB2 protein, human; D000074165:Zinc Finger E-box Binding Homeobox 2