TY - JOUR
T1 - GSTP1 promoter methylation is associated with recurrence in early stage prostate cancer
AU - Maldonado, Leonel
AU - Brait, Mariana
AU - Loyo, Myriam
AU - Sullenberger, Lauren
AU - Wang, Kevin
AU - Peskoe, Sarah B.
AU - Rosenbaum, Eli
AU - Howard, Roslyn
AU - Toubaji, Antoun
AU - Albadine, Roula
AU - Netto, George J.
AU - Hoque, Mohammad O.
AU - Platz, Elizabeth A.
AU - Sidransky, David
N1 - Publisher Copyright:
© 2014 American Urological Association Education and Research, Inc.
PY - 2014/11/1
Y1 - 2014/11/1
N2 - Purpose: Recurrent prostate cancer remains a major problem. Staging, grading and prostate specific antigen level at surgery are helpful but still imperfect predictors of recurrence. For this reason there is an imperative need for additional biomarkers that add to the prediction of currently used prognostic factors.Materials and Methods: We evaluated the extent of promoter methylation of genes previously reported as aberrantly methylated in prostate cancer (AIM1, APC, CCND2, GPX3, GSTP1, MCAM, RARb2, SSBP2 and TIMP3) by quantitative fluorogenic methylation-specific polymerase chain reaction. We used cancer tissue from a nested case-control study of 452 patients surgically treated for prostate cancer. Recurrence cases and controls were compared and the association between methylation extent and recurrence risk was estimated by logistic regression adjusting for patient age at prostatectomy, prostatectomy year, stage, grade, surgical margins and preprostatectomy prostate specific antigen. All statistical tests were 2-sided with p≤0.05 considered statistically significant.Results: The extent of GSTP1 methylation was higher in patients with recurrence than in controls (p = 0.01), especially patients with early disease, ie organ confined or limited extraprostatic extension (p = 0.001). After multivariate adjustment GSTP1 promoter methylation at or above the median was associated with an increased risk of recurrence, including in men with early disease (each p = 0.05).Conclusions: Greater GSTP1 promoter methylation in cancer tissue was independently associated with the risk of recurrence in patients with early prostate cancer. This suggests that GSTP1 promoter methylation may be a potential tissue based recurrence marker.
AB - Purpose: Recurrent prostate cancer remains a major problem. Staging, grading and prostate specific antigen level at surgery are helpful but still imperfect predictors of recurrence. For this reason there is an imperative need for additional biomarkers that add to the prediction of currently used prognostic factors.Materials and Methods: We evaluated the extent of promoter methylation of genes previously reported as aberrantly methylated in prostate cancer (AIM1, APC, CCND2, GPX3, GSTP1, MCAM, RARb2, SSBP2 and TIMP3) by quantitative fluorogenic methylation-specific polymerase chain reaction. We used cancer tissue from a nested case-control study of 452 patients surgically treated for prostate cancer. Recurrence cases and controls were compared and the association between methylation extent and recurrence risk was estimated by logistic regression adjusting for patient age at prostatectomy, prostatectomy year, stage, grade, surgical margins and preprostatectomy prostate specific antigen. All statistical tests were 2-sided with p≤0.05 considered statistically significant.Results: The extent of GSTP1 methylation was higher in patients with recurrence than in controls (p = 0.01), especially patients with early disease, ie organ confined or limited extraprostatic extension (p = 0.001). After multivariate adjustment GSTP1 promoter methylation at or above the median was associated with an increased risk of recurrence, including in men with early disease (each p = 0.05).Conclusions: Greater GSTP1 promoter methylation in cancer tissue was independently associated with the risk of recurrence in patients with early prostate cancer. This suggests that GSTP1 promoter methylation may be a potential tissue based recurrence marker.
KW - biological markers
KW - glutathione S-transferase pi
KW - methylation
KW - neoplasm recurrence, local
KW - prostatic neoplasms
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U2 - 10.1016/j.juro.2014.04.082
DO - 10.1016/j.juro.2014.04.082
M3 - Article
C2 - 24769028
AN - SCOPUS:84906326131
SN - 0022-5347
VL - 192
SP - 1542
EP - 1548
JO - Journal of Urology
JF - Journal of Urology
IS - 5
ER -