Title
Matrix metalloproteinase-9 measured in urine from bladder cancer patients is an independent prognostic marker of poor survival
Author
Offersen, B.V.
Knap, M.M.
Horsman, M.R.
Verheijen, J.
Hanemaaijer, R.
Overgaard, J.
TNO Kwaliteit van Leven
Publication year
2010
Abstract
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.
Subject
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
To reference this document use:
http://resolver.tudelft.nl/uuid:38b918a0-0675-4463-bf19-5c8300ecafec
DOI
https://doi.org/10.3109/0284186x.2010.509109
TNO identifier
425151
ISSN
0284-186X
Source
Acta Oncologica, 49 (8), 1283-1287
Document type
article