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Cystatin B as a tissue and urinary biomarker of bladder cancer recurrence and disease progression.

AbstractPURPOSE:
Using proteomic techniques, we sought to identify novel protein biomarkers in tissue and urine from patients with transitional cell carcinoma (TCC).
EXPERIMENTAL DESIGN:
Urinary and tissue proteomes were analyzed and differentially expressed proteins were identified by mass spectrometry. One of the proteins, cystatin B, was further analyzed in TCC tissue by immunohistochemistry and in urine by semiquantitative Western blot analysis.
RESULTS:
Cystatin B tissue staining intensity significantly increased concordantly with TCC grade (P = 0.0008). Elevated urinary cystatin B levels correlated with increasing tumor grade (P = 0.062) and stage (P = 0.0047). Patients with elevated levels of cystatin B had a shorter mean +/- SE time to disease recurrence (12 +/- 1.82 months) compared with patients who had low levels (28.8 +/- 2.26 months; P = 0.0047). Similarly, patients with elevated cystatin B levels had a shorter time to grade/stage progression compared with patients with low urinary cystatin B (P = 0.0007). By multivariate Cox regression analysis, an elevated cystatin B level was the most significant variable predicting disease recurrence (hazard ratio, 3.8; 95% confidence interval, 1.5-9.5; P = 0.0049) and grade/stage progression (hazard ratio, 10.4; 95% confidence interval, 1.6-201.5; P = 0.0104).
CONCLUSIONS:
Cystatin B is elevated in tissue and urine of bladder cancer patients. Cystatin B urine levels are positively correlated with tumor grade, stage, and shorter time to disease recurrence and progression. Consequently, cystatin B may be useful as a novel predictive biomarker in TCC of the bladder.
AuthorsAdam S Feldman, Jacqueline Banyard, Chin-Lee Wu, W Scott McDougal, Bruce R Zetter
JournalClinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 15 Issue 3 Pg. 1024-31 (Feb 01 2009) ISSN: 1078-0432 [Print] United States
PMID19188175 (Publication Type: Evaluation Study, Journal Article, Research Support, N.I.H., Extramural)
Chemical References
  • Biomarkers, Tumor
  • Cystatin B
Topics
  • Biomarkers, Tumor (urine)
  • Carcinoma, Transitional Cell (metabolism, pathology, urine)
  • Cystatin B (analysis, urine)
  • Disease Progression
  • Humans
  • Protein Array Analysis
  • Recurrence
  • Urinary Bladder Neoplasms (metabolism, pathology, urine)

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