A novel approach to using matrix metalloproteinases for bladder cancer.
OBJECTIVE
Given the steadily growing cancer survivor population, increasing pressure has been placed on more effective clinical approaches and biomarker assays to manage care. For bladder cancer despite the high probability of recurrence the number of patients with recurrent disease is significantly lower than the number that remains cancer free at any monitoring interval. We developed a noninvasive urine assay using a novel approach to identify patients without recurrent cancer with extremely high confidence.


METHODS
Previous studies show that matrix metalloproteinases are increased in the urine of patients with cancer compared to that in disease-free individuals. To determine the clinical usefulness of these markers as monitors for bladder cancer recurrence we measured and compared metalloproteinase-2, metalloproteinase-9 and metalloproteinase-9/neutrophil gelatinase-associated lipocalin by enzyme-linked immunosorbent assay and zymography in a set of 530 samples, including 84 samples from patients with bladder cancer.


RESULTS
Initial studies using urine metalloproteinase to discriminate disease-free patients from those with bladder cancer resulted in 80% sensitivity (67 of 84) and 71% specificity (318 of 446) for metalloproteinase-9. By applying our novel Clinical Intervention Determining Diagnostic() clinical approach to metalloproteinase-9 we correctly identified 42% of cases that were cystoscopy negative with 98% negative predictive value.


CONCLUSIONS
A noninvasive urine diagnostic assay that uses metalloproteinases with the Clinical Intervention Determining Diagnostic could lead to more efficient treatment in bladder cancer survivors by decreasing the number of negative cystoscopies (42%), allowing physicians to more selectively monitor those at high risk.
Fernández
Cecilia A
CA
Predictive Biosciences, Inc, Lexington, Massachusetts, USA.
Wszolek
Matthew F
MF
Loughlin
Kevin R
KR
Libertino
John A
JA
Summerhayes
Ian C
IC
Shuber
Anthony P
AP
D000209:Acute-Phase Proteins / Q000652:urine; D015415:Biomarkers / Q000652:urine; D006801:Humans; D000071068:Lipocalin-2; D054834:Lipocalins / Q000652:urine; D020778:Matrix Metalloproteinase 2 / Q000652:urine*; D020780:Matrix Metalloproteinase 9 / Q000652:urine*; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis* / Q000652:urine; D011237:Predictive Value of Tests; D011518:Proto-Oncogene Proteins / Q000652:urine; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis* / Q000652:urine*
D000209:Acute-Phase Proteins; D015415:Biomarkers; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9