TY - JOUR
T1 - Tissue inhibitor of metalloproteinases-3 promoter methylation is an independent prognostic factor for bladder cancer
AU - Hoque, Mohammad Obaidul
AU - Begum, Shahnaz
AU - Brait, Mariana
AU - Jeronimo, Carmen
AU - Zahurak, Marianna
AU - Ostrow, Kimberly Laskie
AU - Rosenbaum, Eli
AU - Trock, Bruce
AU - Westra, William H.
AU - Schoenberg, Mark
AU - Goodman, Steven N.
AU - Sidransky, David
PY - 2008/2
Y1 - 2008/2
N2 - Purpose: TIMP-3 (tissue inhibitor of metalloproteinases-3) is 1 of 4 members of a family of proteins that were originally classified according to their ability to inhibit matrix metalloproteinases. We analyzed TIMP-3 methylation in 175 urine sediment DNA samples from patients with bladder cancer with well characterized clinicopathological parameters, including patient outcome. Materials and Methods: We examined urine sediment DNA for aberrant methylation of 9 genes, including TIMP-3, by quantitative fluorogenic real-time polymerase chain reaction. Results: Using an optimal cutoff value by TaqMan® quantitation we found that the risk of death was statistically significantly higher in patients with higher TIMP-3 and ARF methylation (HR 1.99, 95% CI 1.12 to 3.27, p = 0.01 and HR 1.66, 95% CI 1.00 to 2.76, p = 0.05, respectively) than in patients without/lower TIMP3 and ARF methylation in urine. A significant correlation was also seen between the risk of death and stage 3 tumor (HR 2.73, 95% CI 1.58 to 4.72, p = 0.003) and metastasis (HR 3.32, 95% CI 1.98 to 5.57, p = 0.0001). Multivariate analysis subsequently revealed that TIMP-3 methylation was an independent prognostic factor for bladder cancer survival with stage and metastasis (p = 0.001 and 0.02, respectively). Conclusions: These results suggest that TIMP-3 promoter methylation could be a clinically applicable marker for bladder cancer progression.
AB - Purpose: TIMP-3 (tissue inhibitor of metalloproteinases-3) is 1 of 4 members of a family of proteins that were originally classified according to their ability to inhibit matrix metalloproteinases. We analyzed TIMP-3 methylation in 175 urine sediment DNA samples from patients with bladder cancer with well characterized clinicopathological parameters, including patient outcome. Materials and Methods: We examined urine sediment DNA for aberrant methylation of 9 genes, including TIMP-3, by quantitative fluorogenic real-time polymerase chain reaction. Results: Using an optimal cutoff value by TaqMan® quantitation we found that the risk of death was statistically significantly higher in patients with higher TIMP-3 and ARF methylation (HR 1.99, 95% CI 1.12 to 3.27, p = 0.01 and HR 1.66, 95% CI 1.00 to 2.76, p = 0.05, respectively) than in patients without/lower TIMP3 and ARF methylation in urine. A significant correlation was also seen between the risk of death and stage 3 tumor (HR 2.73, 95% CI 1.58 to 4.72, p = 0.003) and metastasis (HR 3.32, 95% CI 1.98 to 5.57, p = 0.0001). Multivariate analysis subsequently revealed that TIMP-3 methylation was an independent prognostic factor for bladder cancer survival with stage and metastasis (p = 0.001 and 0.02, respectively). Conclusions: These results suggest that TIMP-3 promoter methylation could be a clinically applicable marker for bladder cancer progression.
KW - Bladder
KW - Bladder neoplasms
KW - Methylation
KW - Tissue inhibitor of metalloproteinase-3
KW - Tumor markers, biological
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U2 - 10.1016/j.juro.2007.09.019
DO - 10.1016/j.juro.2007.09.019
M3 - Article
C2 - 18082200
AN - SCOPUS:38849165454
SN - 0022-5347
VL - 179
SP - 743
EP - 747
JO - Investigative Urology
JF - Investigative Urology
IS - 2
ER -
