You have accessJournal of UrologyProstate Cancer: Basic Research I1 Apr 2015MP37-19 AXIN2 EXPRESSION PREDICTS PROSTATE CANCER RECURRENCE AND MEDIATES AN INVASIVE, TUMORIGENIC PHENOTYPE Brian Hu, Adrian Fairey, Anisha Madhav, Dongyun Yang, Meng Li, Susan Groshen, Craig Stephens, Philip Kim, Navneet Virk, Lina Wang, Sue Ellen Martin, Nicholas Erho, Elai Davicioni, Robert Jenkins, Robert Den, Tong Xu, Yucheng Xu, Inderbir Gill, David Quinn, and Amir Goldkorn Brian HuBrian Hu More articles by this author , Adrian FaireyAdrian Fairey More articles by this author , Anisha MadhavAnisha Madhav More articles by this author , Dongyun YangDongyun Yang More articles by this author , Meng LiMeng Li More articles by this author , Susan GroshenSusan Groshen More articles by this author , Craig StephensCraig Stephens More articles by this author , Philip KimPhilip Kim More articles by this author , Navneet VirkNavneet Virk More articles by this author , Lina WangLina Wang More articles by this author , Sue Ellen MartinSue Ellen Martin More articles by this author , Nicholas ErhoNicholas Erho More articles by this author , Elai DavicioniElai Davicioni More articles by this author , Robert JenkinsRobert Jenkins More articles by this author , Robert DenRobert Den More articles by this author , Tong XuTong Xu More articles by this author , Yucheng XuYucheng Xu More articles by this author , Inderbir GillInderbir Gill More articles by this author , David QuinnDavid Quinn More articles by this author , and Amir GoldkornAmir Goldkorn More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.1282AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Better biomarkers are needed in prostate cancer (PCa) to predict disease recurrence and guide optimal therapy. We investigated whether genes associated with a highly tumorigenic, drug resistant, progenitor phenotype impact PCa biology and clinical outcomes in localized disease. METHODS Radical prostatectomy (RP) specimens (+/- disease recurrence) were analyzed by qRT-PCR to quantify expression of genes associated with self-renewal, drug resistance, and tumorigenicity in prior studies. Univariable and multivariable associations between gene expression and PCa recurrence were confirmed by bootstrap internal validation and by external validation in independent cohorts and in-silico. siRNA knockdown and lentiviral overexpression were used to determine the effect of gene expression on PCa proliferation, invasion and tumor growth. RESULTS Four candidate genes were differentially expressed in PCa recurrence, and of these, low AXIN2 expression was internally validated. In external cohorts and in silico, low AXIN2 was independently associated with more aggressive PCa, biochemical recurrence, and metastasis-free survival after RP. In vitro and in vivo, low AXIN2 expression was associated with a cancer stem-like cell-surface signature, and siRNA knockdown of AXIN2 resulted in significantly greater invasiveness. Conversely, ectopic overexpression of AXIN2 significantly reduced cell proliferation and tumor growth in mice (Figure). CONCLUSIONS Low AXIN2 expression was associated with PCa recurrence after RP in our test population as well as in external validation cohorts, and its expression levels in PCa cells significantly impacted invasiveness, proliferation and tumor growth. Based on these novel roles in PCa, AXIN2 may represent a new putative biomarker and potential therapeutic target in this disease. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e445 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Brian Hu More articles by this author Adrian Fairey More articles by this author Anisha Madhav More articles by this author Dongyun Yang More articles by this author Meng Li More articles by this author Susan Groshen More articles by this author Craig Stephens More articles by this author Philip Kim More articles by this author Navneet Virk More articles by this author Lina Wang More articles by this author Sue Ellen Martin More articles by this author Nicholas Erho More articles by this author Elai Davicioni More articles by this author Robert Jenkins More articles by this author Robert Den More articles by this author Tong Xu More articles by this author Yucheng Xu More articles by this author Inderbir Gill More articles by this author David Quinn More articles by this author Amir Goldkorn More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...