Low circulating levels of ProMMP-2 are associated with adverse prognosis in bladder cancer

Tumour Biol. 2008;29(5):279-86. doi: 10.1159/000156705. Epub 2008 Sep 19.

Abstract

Objectives: In this study the serum levels of proMMP-2, active MMP-2, TIMP-2 and MMP-2:TIMP2 complex were evaluated. We also studied the correlation of these parameters with clinicopathological parameters in patients suffering from bladder carcinoma and outcome in this patient group.

Methods: The levels of circulating proMMP-2, active MMP-2, proMMP-9, TIMP-1, TIMP-2 and MMP-2:TIMP-2 complex of 84 patients with bladder cancer were measured by ELISA. The proMMP-2 and TIMP-2 immunoreactive proteins were studied. These results were compared to clinicopathological parameters and patient outcome.

Results: Low circulating proMMP-2 levels significantly correlated with poor prognosis. The 5-year disease-specific survival rate was 46% in patients with high levels of proMMP-2 versus 23% in patients with low proMMP-2 levels (p = 0.011). Low TIMP-2 levels could also present as a marker of poor prognosis. In this study, the 5-year disease-specific survival in patients with low circulating TIMP-2 levels was 19% compared to 66% in patients with high TIMP-2 levels (p = 0.004).

Conclusion: These results indicate that high levels of circulating proMMP-2 and TIMP-2 levels are both associated with a better clinical course; moreover, total proMMP-2 is an independent prognostic marker of bladder cancer progression.

Publication types

  • Comparative Study

MeSH terms

  • Aged
  • Aged, 80 and over
  • Case-Control Studies
  • Enzyme Precursors / blood*
  • Female
  • Gelatinases / blood*
  • Humans
  • Male
  • Matrix Metalloproteinase 2 / blood*
  • Matrix Metalloproteinase 9 / blood*
  • Middle Aged
  • Neoplasm Recurrence, Local / blood
  • Neoplasm Recurrence, Local / enzymology
  • Neoplasm Recurrence, Local / pathology
  • Prognosis
  • Survival Rate
  • Tissue Inhibitor of Metalloproteinase-1 / blood*
  • Tissue Inhibitor of Metalloproteinase-2 / blood*
  • Urinary Bladder Neoplasms / blood*
  • Urinary Bladder Neoplasms / enzymology
  • Urinary Bladder Neoplasms / pathology

Substances

  • Enzyme Precursors
  • Tissue Inhibitor of Metalloproteinase-1
  • Tissue Inhibitor of Metalloproteinase-2
  • Gelatinases
  • pro-matrix metalloproteinase 9
  • progelatinase
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9