Cancer often involves inflammatory processes. We hypothesized that immune mediators in urine may serve as biomarkers for bladder cancer (BCa).
To investigate whether BCa might be marked by urinary levels of heat shock proteins (HSPs; HSP60, HSP70, or HSP90) or cytokines (interferon [IFN]-γ, tumor necrosis factor [TNF]-α, tumor growth factor [TGF]-β, interleukin [IL]-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, or IL-13).
Design, setting, and participants
This was a case–control study with a discovery and validation phase. We examined urine from 106 consecutive patients: healthy controls (n
We used the area under the curve (AUC) of a receiver operating characteristic analysis to determine the ability of HSPs and cytokines to mark BCa and applied a multivariate logistic regression to create a formula able to diagnose BCa. The formula was applied to the validation set without recalculation, and positive and negative predictive values were calculated.
Results and limitations
Urinary concentrations of IL-8, IL-10, and IL-13 were significantly elevated in BCa; IL-13 was the most prominent marker (AUC: 0.93; 95% confidence interval [CI], 0.85–0.99). The multivariate regression analysis highlighted HSP60 (odds ratio [OR]: 1.206; 95% CI, 1.041–1.397, p
The validation assay was performed using HSP60 and IL-13. The overall positive predictive value was 74% (95% CI, 64–84%); and the negative predictive value was 76% (95% CI, 66–86%). Since we examined a small number of patients, the results need to be confirmed in a larger cohort.
These results suggest that it might be possible to develop a urinary biomarker for BCa and raise the possibility that expression of anti-inflammatory cytokines and HSPs might allow BCa to evade immune surveillance.
Keywords: Biomarkers, Heat shock proteins, Cytokines, Diagnosis, Bladder cancer.
a Institute of Urology, Rabin Medical Center, Beilinson Campus, Petach Tikva, Israel
b Department of Immunology, The Weizmann Institute of Science, Rehovot 76100, Israel
D. Margel and M. Pesvner-Fischer contributed equally to the manuscript.
© 2010 European Association of Urology, Published by Elsevier B.V.