GSTP1 promoter methylation is associated with recurrence in early stage prostate cancer

Leonel Maldonado, Mariana Brait, Myriam Loyo, Lauren Sullenberger, Kevin Wang, Sarah B. Peskoe, Eli Rosenbaum, Roslyn Howard, Antoun Toubaji, Roula Albadine, George J. Netto, Mohammad O. Hoque, Elizabeth A. Platz, David Sidransky

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1542-1548
Number of pages7
JournalJournal of Urology
Volume192
Issue number5
DOIs
StatePublished - Nov 1 2014

Keywords

  • biological markers
  • glutathione S-transferase pi
  • methylation
  • neoplasm recurrence, local
  • prostatic neoplasms

ASJC Scopus subject areas

  • Urology

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    Maldonado, L., Brait, M., Loyo, M., Sullenberger, L., Wang, K., Peskoe, S. B., Rosenbaum, E., Howard, R., Toubaji, A., Albadine, R., Netto, G. J., Hoque, M. O., Platz, E. A., & Sidransky, D. (2014). GSTP1 promoter methylation is associated with recurrence in early stage prostate cancer. Journal of Urology, 192(5), 1542-1548. https://doi.org/10.1016/j.juro.2014.04.082