N-cadherin, a novel prognostic biomarker, drives malignant progression of colorectal cancer

Mol Med Rep. 2015 Aug;12(2):2999-3006. doi: 10.3892/mmr.2015.3687. Epub 2015 Apr 27.

Abstract

Recent studies have indicated that the epithelial-mesenchymal transition (EMT) is a key molecular mechanism involved in the development of colorectal cancer (CRC). N-cadherin is a mesenchymal marker of the EMT and has been closely linked to several human malignancies. However, its role in CRC has remained elusive. In the present study, qRT-PCR and western blot analysis indicated that N-cadherin expression was higher in tumor tissues than in that in their adjacent normal tissues. Immunohistochemical evaluation of N-cadherin and E-cadherin (an epithelial marker of the EMT), indicated that N-cadherin expression was significantly associated with tumor differentiation, tumor size as well as tumor, nodes and metastasis stage. Correlation analysis suggested the expression of N-cadherin was negatively correlated with that of E-cadherin in CRC tissues. Kaplan-Meier analysis indicated that patients with high N-cadherin expression had a significantly lower overall survival and disease-free survival rate than those with low N-cadherin expression, while the opposite was found for E-cadherin. Of note, the present study found that high N-cadherin expression was an independent prognostic factor for CRC. In vitro assays showed that N-cadherin was widely expressed in CRC cell lines and silencing of N-cadherin suppressed the proliferation and migration of the CRC cell line HT-29 by upregulating E-cadherin, suggesting a potential role of N-cadherin in inducing EMT. In conclusion, the present study suggested that N-cadherin has the potential of serving as a novel prognostic predictor and a promising therapeutic target for CRC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Cadherins / antagonists & inhibitors
  • Cadherins / genetics
  • Cadherins / metabolism*
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Colorectal Neoplasms / diagnosis
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / pathology*
  • Disease-Free Survival
  • Epithelial-Mesenchymal Transition
  • Female
  • HCT116 Cells
  • HT29 Cells
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Prognosis
  • RNA Interference
  • RNA, Small Interfering / metabolism
  • Real-Time Polymerase Chain Reaction
  • Up-Regulation

Substances

  • Biomarkers, Tumor
  • Cadherins
  • RNA, Small Interfering