title: Matrix metalloproteinase-7 as a marker of metastasis and predictor of poor survival in bladder cancer.
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.
authors.affiliation: Department of Urology, University of Duisburg-Essen, Essen, Germany. sztibusz@gmail.com
authors.forename: Tibor
authors.initials: T
authors.lastname: Szarvas
authors.forename: Markus
authors.initials: M
authors.lastname: Becker
authors.forename: Frank
authors.initials: F
authors.lastname: vom Dorp
authors.forename: Carolin
authors.initials: C
authors.lastname: Gethmann
authors.forename: Martin
authors.initials: M
authors.lastname: Tötsch
authors.forename: Agnes
authors.initials: A
authors.lastname: Bánkfalvi
authors.forename: Kurt W
authors.initials: KW
authors.lastname: Schmid
authors.forename: Imre
authors.initials: I
authors.lastname: Romics
authors.forename: Herbert
authors.initials: H
authors.lastname: Rübben
authors.forename: Süleyman
authors.initials: S
authors.lastname: Ergün
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D020783:Matrix Metalloproteinase 7 / Q000032:analysis* / Q000097:blood / Q000235:genetics; D008875:Middle Aged; D015999:Multivariate Analysis; D009362:Neoplasm Metastasis; D001749:Urinary Bladder Neoplasms / Q000401:mortality / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor; C060932:MMP7 protein, human; D020783:Matrix Metalloproteinase 7