Matrix metalloproteinase-7 as a marker of metastasis and predictor of poor survival in bladder cancer

Cancer Sci. 2010 May;101(5):1300-8. doi: 10.1111/j.1349-7006.2010.01506.x. Epub 2010 Jan 20.

Abstract

Matrix metalloproteinases (MMPs) play an important role in tumor progression and metastasis. Here, we investigated the prognostic relevance of MMP-7 in urinary bladder cancer. MMP-7 gene expression was measured in tissue samples of 101 patients using quantitative real-time PCR. Circulating MMP-7 serum levels of 98 individuals (79 patients and 19 controls) were analyzed by enzyme-linked immunosorbent assay. The results were compared with the clinical follow-up data, performing Kaplan-Meier log-rank test as well as univariate and multivariate Cox analysis. In representative cases, immunohistochemical analysis for MMP-7 was performed. We detected significantly elevated MMP-7 levels both in tissue and serum samples of patients with metastatic disease (P = 0.001 and P = 0.002). Multivariate analysis revealed that high MMP-7 tissue expression and serum concentration are stage- and grade-independent predictors of both metastasis-free (hazard ratio [HR] = 3.80, 95% confidence interval [CI], 1.29-11.23, P = 0.016, and HR = 2.53, 95% CI, 1.01-6.37, P = 0.048) and disease-specific survival (HR = 1.89, 95% CI, 1.00-3.55, P = 0.050 and HR = 1.95, 95% CI, 1.03-3.71, P = 0.041). Based on these findings, we conclude that MMP-7 is a promising marker to detect present and to predict future metastasis. Serum MMP-7 analysis provides information about the risk of metastasis before surgery which could help to optimize therapeutic procedures. Furthermore, high MMP-7 tissue and/or serum levels could identify patients most likely to benefit from early adjuvant chemotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / analysis*
  • Female
  • Humans
  • Immunohistochemistry
  • Male
  • Matrix Metalloproteinase 7 / analysis*
  • Matrix Metalloproteinase 7 / blood
  • Matrix Metalloproteinase 7 / genetics
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Metastasis
  • Urinary Bladder Neoplasms / mortality
  • Urinary Bladder Neoplasms / pathology*

Substances

  • Biomarkers, Tumor
  • MMP7 protein, human
  • Matrix Metalloproteinase 7