MP28-14 DECREASED EXPRESSION OF MALE SPECIFIC HISTONE DEMETHYLASE “KDM5D” IS PROGNOSTIC FOR DEVELOPMENT OF CASTRATION-RESISTANT PROSTATE CANCER

You have accessJournal of UrologyProstate Cancer: Markers I1 Apr 2017MP28-14 DECREASED EXPRESSION OF MALE SPECIFIC HISTONE DEMETHYLASE “KDM5D” IS PROGNOSTIC FOR DEVELOPMENT OF CASTRATION-RESISTANT PROSTATE CANCER Kazumasa Komura, Seong Ho Jeong, Haruhito Azuma, Gwo-Shu Lee, Christopher Sweeney, and Philip Kantoff Kazumasa KomuraKazumasa Komura More articles by this author , Seong Ho JeongSeong Ho Jeong More articles by this author , Haruhito AzumaHaruhito Azuma More articles by this author , Gwo-Shu LeeGwo-Shu Lee More articles by this author , Christopher SweeneyChristopher Sweeney More articles by this author , and Philip KantoffPhilip Kantoff More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.827AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES We previously showed that decreased expression of the Lysine-Specific Demethylase ′KDM5D′ encoded on the Y chromosome was associated with docetaxel resistance (Komura et al, 2016, PNAS). We hypothesize that loss of KDM5D may significantly affect the epigenetic landscape in prostate cancer cells and facilitate the development of CRPC. METHODS To elucidate biological function of KDM5D, we performed RNAseq analysis in hormone sensitive LNCaP cells (KDM5D positive) and corresponding LNCaP-104R2 CRPC cells (KDM5D negative). Individual genes which were found as potential targets of KDM5D were further explored in a publically available clinical database. RESULTS We found 143 overlapping genes, which are upregulated by knockdown of KDM5D in LNCaP and down regulated by overexpression of KDM5D in 104R2 and 28 genes, which were down regulated by KDM5D knockdown in LNCaP and up-regulated by KDM5D overexpression in 104R2. Gene ontology (GO) analyses with FDR<0.05 from the 143 genes identified mitotic and cell cycle related genes as most commonly upregulated by loss of KDM5D (Figure 1). To validate the results, we explored the Taylor′s prostate cancer cohort with cBioportal. Of 8643 genes negatively correlated with KDM5D expression level (Pearson Correlation Coefficient < -0.3), 69 genes were identified in both our data and the Taylor′s cohort. Upregulation of these genes in CRPC was further confirmed in 2 publicly available datasets (PAD).2 (Figure 2). Finally in a PAD from a Mayo Clinic′s cohort (Illumina DASL Cancer Panel microarray) which included 8 genes out of the 69 genes, noted shorter cancer-specific mortality in pts with higher expression of those genes was demonstrated in all 8 genes. CONCLUSIONS Loss of KDM5D is associated with upregulation of mitotic and cell-cycle related genes which may lead to development of CRPC and serve as prognostic factor for its development. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e343-e344 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Kazumasa Komura More articles by this author Seong Ho Jeong More articles by this author Haruhito Azuma More articles by this author Gwo-Shu Lee More articles by this author Christopher Sweeney More articles by this author Philip Kantoff More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...