MP37-17 DISTINCT EXPRESSION FEATURES OF PMEPA1 AND ITS ISOFORM STAG1 IN PROSTATE CANCER

Abstract

You have accessJournal of UrologyProstate Cancer: Basic Research I1 Apr 2015MP37-17 DISTINCT EXPRESSION FEATURES OF PMEPA1 AND ITS ISOFORM STAG1 IN PROSTATE CANCER Hua Li, Lakshmi Ravindranath, Yongmei Chen, David McLeod, Isabell Sesterhenn, Albert Dobi, Shiv Srivastava, and Gyorgy Petrovics Hua LiHua Li More articles by this author , Lakshmi RavindranathLakshmi Ravindranath More articles by this author , Yongmei ChenYongmei Chen More articles by this author , David McLeodDavid McLeod More articles by this author , Isabell SesterhennIsabell Sesterhenn More articles by this author , Albert DobiAlbert Dobi More articles by this author , Shiv SrivastavaShiv Srivastava More articles by this author , and Gyorgy PetrovicsGyorgy Petrovics More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.1280AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Our earlier studies defined PMEPA1, a NEDD4 E3 ubiquitin ligase binding protein, as an androgen regulated gene with decreased or absent PMEPA1 transcripts in 65% of prostate cancer (CaP). Solid tumor associated gene 1 (STAG1) is an isoform of PMEPA1 upregulated in several solid tumors. STAG1 has an alternative first exon and a predicted alternative promoter compared to PMEPA1. In order to better understand STAG1 and its relation to PMEPA1 in CaP, this study focuses on comparative analyses of STAG1 and PMEPA1 expression in human CaP. METHODS Tumor and benign epithelial cells were laser capture microdissected (LCM) from frozen OCT embedded prostate tissue. Total RNA was isolated from the LCM samples and converted to cDNA. Quantitative gene expression analysis was performed by TaqMan-based QRT-PCR. A total of 117 matched normal and prostate tumor specimens (N=234) were assayed for STAG1, PMEPA1, AR and PSA transcripts. Correlation of the gene expression data with clinical and pathological characteristics were examined by Kaplan-Meier survival and Cox proportional hazard model analyses. Biochemical recurrence (BCR) was defined as two consecutive post-operative PSA > 0.2 ng/mL 2 months after surgery. RESULTS STAG1 mRNA levels did not have significant correlation with transcript levels of PMEPA1, AR or PSA. Patients with increased tumor / normal STAG1 mRNA level had a shorter time to BCR in a Kaplan-Meier analysis (P=0.018). The correlation of increased STAG1 expression in tumor cells with increased chance for BCR was supported by multivariable Cox proportional hazard model (P=0.0015; HR=4.3). CONCLUSIONS In contrast to PMEPA1, STAG1 expression does not appear to be androgen regulated. Surprisingly, STAG1 expression was an independent predictor of BCR after radical prostatectomy. Based on our findings further mechanistic evaluation of STAG1 and PMEPA1 in CaP is warranted. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e444 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Hua Li More articles by this author Lakshmi Ravindranath More articles by this author Yongmei Chen More articles by this author David McLeod More articles by this author Isabell Sesterhenn More articles by this author Albert Dobi More articles by this author Shiv Srivastava More articles by this author Gyorgy Petrovics More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...