Aminopeptidase activities as prospective urinary biomarkers for bladder cancer Journal Article

Authors: Taylor, J. M.; Yaneva, M.; Velasco, K.; Philip, J.; Erdjument-Bromage, H.; Ostrovnaya, I.; Lilja, H. G.; Bochner, B. H.; Tempst, P.
Article Title: Aminopeptidase activities as prospective urinary biomarkers for bladder cancer
Abstract: Purpose: Proteases have been implicated in cancer progression and invasiveness. We have investigated the activities, as opposed to simple protein levels, of selected aminopeptidases in urine specimens to serve as potential novel biomarkers for urothelial cancer. Experimental design: The unique urinary proteomes of males and females were profiled to establish the presence of a gender-independent set of aminopeptidases. Samples were also collected from patients with urothelial cancer and matched controls. A SOP for urine processing was developed taking into account hydration variation. Five specific aminopeptidase activity assays, using fluorophoric substrates, were optimized for evaluation of marker potential. Results: Nineteen exopeptidases and 21 other proteases were identified in urine and the top-five most abundant aminopeptidases, identical in both genders, selected for functional studies. Depending on the enzyme, activities were consistently lower (p ≤ 0.05), higher or unchanged in the cancer samples as compared to controls. Two selected aminopeptidase activities used as a binary classifier resulted in a ROC curve with an AUC = 0.898. Conclusion and clinical relevance: We have developed functional assays that characterize aminopeptidase activities in urine specimens with adequate technical and intraindividual reproducibility. With further testing, it could yield a reliable biomarker test for bladder cancer detection or prognostication. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Keywords: clinical article; controlled study; area under the curve; cancer growth; sensitivity and specificity; reproducibility; prostate specific antigen; proteome; fluorescence; enzyme activity; bladder cancer; tumor marker; urine; reliability; sex difference; urinalysis; transitional cell carcinoma; hydration; receiver operating characteristic; tumor invasion; bestatin; aminopeptidase; cancer prognosis; human; male; female; priority journal; article; activity biomarkers; aminopeptidases; amastatin
Journal Title: Proteomics Clinical Applications
Volume: 8
Issue: 5-6
ISSN: 1862-8346
Publisher: Wiley V C H Verlag Gmbh  
Date Published: 2014-06-01
Start Page: 317
End Page: 326
Language: English
DOI: 10.1002/prca.201300118
PROVIDER: scopus
PMCID: PMC4059539
PUBMED: 24591208
Notes: Proteomics Clin. Appl. -- Cited By (since 1996):1 -- Export Date: 8 July 2014 -- Source: Scopus
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MSK Authors
  1. Hans Gosta Lilja
    286 Lilja
  2. Paul J Tempst
    307 Tempst
  3. Mariana M Yaneva
    9 Yaneva
  4. Jennifer Marie Taylor
    11 Taylor
  5. Bernard Bochner
    324 Bochner
  6. John Philip
    20 Philip