PRUNE2 and PCA3 Expression in Paired Non-Malignant and Tumor Specimens from Radical Prostatectomy Patients with Gleason Score 7 Prostate Cancer.

Richard C. Lauer,Marc Barry,Jin Wu,Ji-Hyun Lee,Dennis J. McCance,Ruofei Du,Arpit Rao,Andrey S. Dobroff,Emmanuel Dias-Neto,Isan Chen,Renata Pasqualini,Wadih Arap

Journal of Clinical Oncology（2017）SCI 1区

University of New Mexico Comprehensive Cancer Center | University of New Mexico School of Medicine | International Research Center | Mbrace Therapeutics

Cited 1|Views55

Abstract

e16582 Background: PCA3 is an FDA-approved biomarker for prostate cancer. We have recently reported that PRUNE2 is a tumor suppressor gene in human prostate cancer that it is inactivated through a PCA3-mediated regulatory axis. Based upon this previous work, here we investigated if PRUNE2 and PCA3expression levels would be different in non-malignant versus tumor paired samples obtained from Gleason 7 Score prostate cancer patients undergoing radical prostatectomy. Methods: We examined Gleason Score 7 prostate cancer specimens, obtained from a cohort of patients (n=24) who have undergone radical prostatectomy at UNM Hospital. Paired non-malignant and tumor tissues were recovered from these specimens after tissue microdissection and processed for RNA extraction. PRUNE2 and PCA3transcripts were measured by qRT-PCR using three and two different primer sets, respectively, and normalized using appropriate internal controls. Each experiment was carried out in triplicates. The Wilcoxon signed rank test was used to test whether the differences between the paired tumor and non-malignant tissue samples were significant. Results: Gene expression analyses showed PRUNE2 levels to be consistently lower in tumor samples compared to non-malignant areas of the same gland (P<0.0001). In contrast, the opposite trend was seen for PCA3, which has a marked upregulation in tumor areas (P<0.0001). Conclusions: Both PRUNE2 and PCA3 expression levels were significantly different between matched non-malignant and malignant tissue pairs in Gleason Score 7 prostate cancer patients post radical prostatectomy. This retrospective dataset provides additional support for a mechanistic role for the molecular interplay between PRUNE2 and PCA3 in human prostate cancer, which may lead to the development of novel diagnostic and therapeutic approaches in this disease. Prospective studies targeting our original finding are either ongoing or planned. [Table: see text]

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