Wnt1 overexpression promotes tumour progression in non-small cell lung cancer

Eur J Cancer. 2008 Nov;44(17):2680-8. doi: 10.1016/j.ejca.2008.08.004. Epub 2008 Sep 13.

Abstract

Background: The Wnt gene family is involved in embryogenesis and tumourigenesis. We investigated the clinical significance of Wnt1 expression in non-small cell lung cancer (NSCLC).

Method: We studied 216 NSCLC patients. Immunohistochemistry was performed to investigate the Wnt1 expression in relation to the expression of beta-catenin and Wnt-targets, including c-Myc, Cyclin D1, VEGF-A and MMP-7. The Ki-67 proliferation index and the intratumoural microvessel density (IMD) were also evaluated.

Results: The ratio of tumours with an aberrant beta-catenin expression was significantly higher in Wnt1-positive tumours than in Wnt1-negative tumours (p<0.0001). The Wnt1 expression significantly correlated with the expression of c-Myc (p<0.0001), Cyclin D1 (p<0.0001), VEGF-A (p=0.0160), MMP-7 (p<0.0001), the Ki-67 index (p=0.0048) and the IMD (p=0.0267). Furthermore, the Wnt1 status was a significant prognostic factor for NSCLC patients (p=0.0127).

Conclusions: The Wnt1 overexpression is associated with the expression of tumour-associated Wnt-targets, tumour proliferation, angiogenesis and a poor prognosis in NSCLCs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Non-Small-Cell Lung / blood supply
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Cell Proliferation
  • Cyclin D1 / metabolism
  • Humans
  • Immunohistochemistry
  • Lung Neoplasms / blood supply
  • Lung Neoplasms / metabolism*
  • Male
  • Matrix Metalloproteinase 7 / metabolism
  • Microcirculation
  • Middle Aged
  • Neovascularization, Pathologic
  • Prognosis
  • Proto-Oncogene Proteins c-myc / metabolism
  • Vascular Endothelial Growth Factor A / metabolism
  • Wnt1 Protein / metabolism*
  • beta Catenin / metabolism

Substances

  • Proto-Oncogene Proteins c-myc
  • Vascular Endothelial Growth Factor A
  • WNT1 protein, human
  • Wnt1 Protein
  • beta Catenin
  • Cyclin D1
  • Matrix Metalloproteinase 7