MP66-01 NON-PLAQUE PENILE TISSUES FROM MEN WITH PEYRONIE’s DISEASE EXHIBIT EPIGENETIC AND GENE EXPRESSION CHANGES

You have accessJournal of UrologySexual Function/Dysfunction: Basic Research & Pathophysiology (MP66)1 May 2024MP66-01 NON-PLAQUE PENILE TISSUES FROM MEN WITH PEYRONIE's DISEASE EXHIBIT EPIGENETIC AND GENE EXPRESSION CHANGES Ben Christensen, Jessica Schardein, Hunter Levis, Masaya Jimbo, Kelli Gross, Jim Hotaling, Jordan Moore, Seth Parks, Maliha Tasnim, Brendan Olson, Robert Bowles, Tim Jenkins, and Alexander W. Pastuszak Ben ChristensenBen Christensen , Jessica SchardeinJessica Schardein , Hunter LevisHunter Levis , Masaya JimboMasaya Jimbo , Kelli GrossKelli Gross , Jim HotalingJim Hotaling , Jordan MooreJordan Moore , Seth ParksSeth Parks , Maliha TasnimMaliha Tasnim , Brendan OlsonBrendan Olson , Robert BowlesRobert Bowles , Tim JenkinsTim Jenkins , and Alexander W. PastuszakAlexander W. Pastuszak View All Author Informationhttps://doi.org/10.1097/01.JU.0001009468.01097.19.01AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Peyronie's Disease (PD) can significantly impact sexual function. Our group previously established a strong hereditary component to PD, suggesting that genetic variants and/or expression differences may exist which predispose to the disease. Identification of changes in epigenetic and gene expression profiles will facilitate a deeper understanding of the disease and provide insight for more targeted therapies. METHODS: Penile tunica albuginea samples from normal appearing tissue were obtained from men with PD undergoing penile prosthesis placement. Control samples were collected from men with erectile dysfunction (ED) without PD undergoing penile prosthesis placement. DNA methylation analyses were performed on homogenized penile tissue samples via an Illumina Human MethylationEPIC BeadChip v2 array. Differentially methylated regions (DMR) were identified using USEQ with a threshold Wilcoxon FDR score of 40. Gene expression levels were examined in PD and ED samples via RNA-sequencing. RESULTS: A total of 24 tissue samples were collected: 12 ED and 12 PD. USEQ yielded 36 total DMRs with an FDR score of 40 or greater (p-value <0.0001). Of these 36 DMRs, a Stanford GREAT analysis revealed 60 total gene-region associations and five implicated biological processes: anterior/posterior pattern specification, chordate embryonic development, embryo development (ending in birth or egg hatching), somitogenesis, and pattern specification process. Furthermore, differential gene expression analysis identified 76 genes with significant expression changes between PD and ED groups, of which 17 genes were upregulated while 59 were downregulated. Long noncoding RNAs and the keratocan gene showed notable expression differences between PD and ED groups. GO enrichment analysis revealed significant terms related to DNA binding and protein binding. However, none of the differentially regulated genes overlapped with identified DMRs. CONCLUSIONS: This study identified distinct gene expression and DNA methylation patterns between PD and ED groups, despite PD samples originating from non-plaque regions, suggesting that systemic changes may be present. Upregulated genes in PD included long noncoding RNAs and the keratocan gene, suggesting their involvement in disease pathogenesis. Long noncoding RNA overexpression may serve a regulatory function in gene expression or cell processes while overexpression of the keratocan gene may promote collagen accumulation and remodeling, leading to fibrous plaque formation. Likewise, DMRs and their region-gene associations suggest a role in early embryonic development for pathogenesis. Although RNA-seq did not identify significant differentially expressed genes that overlapped with gene-region associations correlated with DMRs, the significance and quantity of DMRs between ED and PD sample groups is indicative of affected biological processes that manifest in distinct pathophysiologies. Further research is needed to investigate if differentially regulated genes exist in DMRs that exhibited changes but did not meet the criteria threshold for inclusion here. Source of Funding: NIH R01 DK126903 to A.W.P.AUA Care Foundation Award to J.S © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e1086 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Ben Christensen More articles by this author Jessica Schardein More articles by this author Hunter Levis More articles by this author Masaya Jimbo More articles by this author Kelli Gross More articles by this author Jim Hotaling More articles by this author Jordan Moore More articles by this author Seth Parks More articles by this author Maliha Tasnim More articles by this author Brendan Olson More articles by this author Robert Bowles More articles by this author Tim Jenkins More articles by this author Alexander W. Pastuszak More articles by this author Expand All Advertisement PDF downloadLoading ...