The c-MET Network as Novel Prognostic Marker for Predicting Bladder Cancer Patients with an Increased Risk of Developing Aggressive Disease

PLoS One. 2015 Jul 30;10(7):e0134552. doi: 10.1371/journal.pone.0134552. eCollection 2015.

Abstract

Previous studies have shown that c-MET is overexpressed in cases of aggressive bladder cancer (BCa). Identification of crosstalk between c-MET and other RTKs such as AXL and PDGFR suggest that c-MET network genes (c-MET-AXL-PDGFR) may be clinically relevant to BCa. Here, we examine whether expression of c-MET network genes can be used to identify BCa patients at increased risk of developing aggressive disease. In vitro analysis, c-MET knockdown suppressed cell proliferation, invasion, and migration, and increased sensitivity to cisplatin-induced apoptosis. In addition, c-MET network gene (c-MET, AXL, and PDGFR) expression allowed discrimination of BCa tissues from normal control tissues and appeared to predict poor disease progression in non-muscle invasive BCa patients and poor overall survival in muscle invasive BCa patients. These results suggest that c-MET network gene expression is a novel prognostic marker for predicting which BCa patients have an increased risk of developing aggressive disease. These genes might be a useful marker for co-targeting therapy, and are expected to play an important role in improving both response to treatment and survival of BCa patients.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Apoptosis / drug effects
  • Biomarkers, Tumor / genetics*
  • Cisplatin / therapeutic use
  • Disease Progression
  • Down-Regulation
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / metabolism
  • Middle Aged
  • Prognosis
  • Proto-Oncogene Proteins c-met / genetics*
  • Receptors, Platelet-Derived Growth Factor / genetics
  • Tumor Cells, Cultured
  • Tumor Suppressor Proteins / genetics
  • Urinary Bladder Neoplasms / drug therapy
  • Urinary Bladder Neoplasms / pathology*
  • Urinary Bladder Neoplasms / surgery

Substances

  • Biomarkers, Tumor
  • PDGFRL protein, human
  • Tumor Suppressor Proteins
  • Proto-Oncogene Proteins c-met
  • Receptors, Platelet-Derived Growth Factor
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9
  • Cisplatin