Evaluation of PRUNE2 and PCA3 expression as metastasis predictors in Gleason 7 prostate cancer.

Abstract

e16583 Background: There is an urgent need to differentiate from truly localized prostate cancer and micrometastatic disease. PCA3 is an FDA-approved biomarker for prostate cancer; however, it is not a predictor of metastasis behavior. We have recently identified PRUNE2 as an unrecognized tumor suppressor gene. Here we examined if the ratio of PRUNE2 and its corresponding dominant-negative oncogene PCA3 might serve as a better predictor of the metastatic potential of prostate cancer, compared to PCA3alone. Methods: We studied 105 prostate cancer patients who underwent a radical prostatectomy at UNM Hospital from 2001 to 2009. At the time of prostatectomy, these patients had a Gleason score of 7 and organ-confined disease. They had at least 5-year follow-up for disease recurrence, and 19 patients developed recurrent disease. PCA3 and PRUNE2 gene expression was quantified by qRT-PCR and normalized to housekeeping control genes. Each experiment was carried out in triplicates. The Wilcoxon rank sum test was used to evaluate whether or not the difference in gene expression of PRUNE2 or PCA3 or the gene expression ratio ( PRUNE2/ PCA3), between patients with and without recurrence, was significant. The association between the time to recurrence and expression levels of each single gene or ratio were also analyzed by the Kaplan-Meier method along with log-rank test and the COX PH modeling. Results: There was no significant difference in expression levels of PRUNE2, PCA3, or the ratio PRUNE2/ PCA3, between patients who developed recurrent disease relative to those who did not. Conclusions: PRUNE2 and PCA3 expression levels, as well as PRUNE2/ PCA3 ratio, did not predict the metastatic potential of Gleason 7 prostate cancer in our retrospective patient cohort. We postulated that the deregulation of the molecular axis of PRUNE2 and PCA3 might occur early in the development of prostate cancer. We are currently examining this mechanistic hypothesis in other studies. [Table: see text]