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Matrix metalloproteinase-9 measured in urine from bladder cancer patients is an independent prognostic marker of poor survival

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Author: Offersen, B.V. · Knap, M.M. · Horsman, M.R. · Verheijen, J. · Hanemaaijer, R. · Overgaard, J.
Institution: TNO Kwaliteit van Leven
Source:Acta Oncologica, 8, 49, 1283-1287
Identifier: 425151
doi: doi:10.3109/0284186X.2010.509109
Keywords: Health · Biomedical Research · creatinine · gelatinase B · adult · aged · article · bladder cancer · cancer mortality · cancer size · cancer survival · clinical assessment · correlation analysis · creatinine blood level · diagnostic value · female · human · major clinical study · male · overall survival · predictive validity · priority journal · prognosis · urinalysis


Introduction. Matrix metalloproteinase 9 (MMP-9) is an endopeptidase involved in various cellular processes, such as tumour development and metastatic spread. In biological samples, MMP-9 can occur as pro-MMP-9 and active MMP-9, or these factors complexed with the inhibitor TIMP-1. An assay, which can measure active and total MMP-9 in biological samples, has been used on the urine from bladder cancer patients and demonstrated a significant correlation between MMP-9 and clinical parameters. The prognostic value of these measurements has never been investigated. Using this assay we have investigated the prognostic influence of total and active MMP-9 in urine from bladder cancer patients. Material and methods. Fresh voided urines from 188 consecutive patients diagnosed with bladder cancer were collected and frozen at diagnosis. After 15 years follow-up 13 patients were still alive, and 175 patients had died. MMP-9 was measured with an immunocapture activity assay. Results. Median MMP-9total was 173.7 units/10 g creatinine (range 034 792), and median MMP-9active was 14 units/10g creatinine (range, 0294 757). The two factors were correlated (Spearmańs rho 0.74, p<0.0001). High MMP-9total and MMP-9active were significantly correlated with large tumour size and poor malignancy grade. Increasing tertiles of MMP-9total and MMP-9active were associated with poor overall survival (p<0.0001 and p=0.003, respectively). A Cox multivariate analysis using death as endpoint identified high tertiles of MMP-9total as independent prognostic markers with a relative risk 2.25 (95% confidence interval, 1.533.30). Conclusion. MMP-9 measured in urine from bladder cancer patients was a strong independent prognostic marker of poor survival. This is the first time high levels of MMP-9 measured in urine from bladder cancer patients have been linked to poor prognosis. This may reflect MMP-9 playing a role in tumour invasion and metastasis. It may be possible to non-invasively measure tumour response to therapy and identify possible tumour recurrence in an early phase. © 2010 Informa Healthcare.