Cystatin B as a tissue and urinary biomarker of bladder cancer recurrence and disease progression.
OBJECTIVE
Using proteomic techniques, we sought to identify novel protein biomarkers in tissue and urine from patients with transitional cell carcinoma (TCC).


METHODS
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.
Feldman
Adam S
AS
Department of Urology, Massachusetts General Hospital, Boston, Massachusetts, USA.
Banyard
Jacqueline
J
Wu
Chin-Lee
CL
McDougal
W Scott
WS
Zetter
Bruce R
BR
D014408:Biomarkers, Tumor / Q000652:urine; D002295:Carcinoma, Transitional Cell / Q000378:metabolism* / Q000473:pathology / Q000652:urine*; D055313:Cystatin B / Q000032:analysis* / Q000652:urine; D018450:Disease Progression; D006801:Humans; D040081:Protein Array Analysis; D012008:Recurrence; D001749:Urinary Bladder Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000652:urine*
D014408:Biomarkers, Tumor; D055313:Cystatin B