Validation of Circulating MMP-7 Level as an Independent Prognostic Marker of Poor Survival in Urinary Bladder Cancer
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Molecular marker analyses aiming a more accurate disease characterization and risk stratification of cancer patients provided several promising marker candidates in the last few years. However, recent reviews underlined the paramount importance of validation, since many of the initially promising results could not be confirmed in independent patient cohorts. If serum or plasma is a more appropriate sample to test for prognostic markers is a matter of debate. We recently found serum MMP-7 levels to correlate with poor patients’ prognosis in urinary bladder cancer. In this study, we examined associations of the MMP-7 plasma levels with clinical follow-up data in an independent cohort of bladder cancer patients to validate our former results and to assess if plasma is also suitable for MMP-7 analysis. Plasma levels of 97 patients and 22 controls were analyzed, using enzyme-linked immunosorbent assay. Associations between MMP-7 plasma concentrations and clinical data were assessed applying both univariate and multivariate analysis. Plasma MMP-7 levels were significantly higher in patients than in controls. Similarly to our former findings in sera, high MMP-7 plasma levels proved to be significant and independent predictors of both overall and disease-specific survival. In addition, we observed a metastasis-specific difference in MMP-7 levels between serum and plasma. In summary, we confirmed the prognostic relevance of circulating MMP-7 levels in an independent cohort of patients and concluded that circulating MMP-7 levels may help to identify bladder cancer patients at high-risk of disease progression who could benefit from an adjuvant chemotherapy or from an extended lymph node dissection.
KeywordsBladder cancer MMP-7 Matrilysin Metastasis Plasma Prognosis Serum
We thank Ms. Stephanie Abraham for excellent technical assistance. We are grateful for the financial assistance of the National Federal Ministry of Education and Research (Project 0313659B).
Conflict of Interests Statement
None of the authors of this manuscript have a conflict of interest to declare.
- 4.Dyrskjøt L, Zieger K, Real FX, Malats N, Carrato A, Hurst C, Kotwal S, Knowles M, Malmström PU, de la Torre M, Wester K, Allory Y, Vordos D, CaillaultA RF, Hein AM, Jensen JL, Jensen KM, Marcussen N, Orntoft TF (2007) Gene expression signatures predict outcome in non-muscle-invasive bladder carcinoma: a multicenter validation study. Clin Cancer Res 13:3545–3551PubMedCrossRefGoogle Scholar
- 10.Eble JN, Epstein JI, Sesterhenn I (2004) World Health Organization classification of tumors. Pathology and genetics of tumors of the urinary system and male genital organs. IARCC Press, Lyon, pp 89–158Google Scholar
- 18.Yamamoto H, Itoh F, Iku S, Adachi Y, Fukushima H, Sasaki S, Mukaiya M, Hirata K, Imai K (2001) Expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases in human pancreatic adenocarcinomas: clinicopathologic and prognostic significance of matrilysin expression. J Clin Oncol 19:1118–1127PubMedGoogle Scholar
- 20.Maurel J, Nadal C, Garcia-Albeniz X, Gallego R, Carcereny E, Almendro V, Mármol M, Gallardo E, Augé JM, Longarón R, Martínez-Fernandez A, Molina R, Castells A, Gascón P (2007) (2007) Serum matrix metalloproteinase 7 levels identifies poor prognosis advanced colorectal cancer patients. Int J Cancer 121:1066–1071PubMedCrossRefGoogle Scholar
- 23.Szarvas T, Becker M, vom Dorp F, Meschede J, Scherag A, Bánkfalvi A, Henning R, Schmid KW, Romics I, Rübben H, Ergün S (2010) Elevated serum matrix metalloproteinase 7 levels predict poor prognosis after radical prostatectomy Int J Cancer (In press)Google Scholar
- 24.Szarvas T, Singer BB, Becker M, vom Dorp F, Jäger T, Szendrői A, Riesz P, Romics I, Rübben H, Ergün S (2010) Urinary MMP-7 level is associated with the presence of metastasis in bladder cancer. BJU Int (In press)Google Scholar