PD46-06 SYMPTOMATIC BENIGN PROSTATIC HYPERPLASIA WITH IMMUNE-ENRICHED LANDSCAPES SHOW LOWER INCIDENCE OF PROSTATE CANCER DEVELOPMENT

Abstract

You have accessJournal of UrologyCME1 May 2022PD46-06 SYMPTOMATIC BENIGN PROSTATIC HYPERPLASIA WITH IMMUNE-ENRICHED LANDSCAPES SHOW LOWER INCIDENCE OF PROSTATE CANCER DEVELOPMENT Nimrod Barashi Gozal, Tiandao Li, Bo Zhang, Charles Nottingham, Gerald Andriole, Kiran Mahajan, and Eric Kim Nimrod Barashi GozalNimrod Barashi Gozal More articles by this author , Tiandao LiTiandao Li More articles by this author , Bo ZhangBo Zhang More articles by this author , Charles NottinghamCharles Nottingham More articles by this author , Gerald AndrioleGerald Andriole More articles by this author , Kiran MahajanKiran Mahajan More articles by this author , and Eric KimEric Kim More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002614.06AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The association between benign prostatic hyperplasia (BPH) and prostate cancer (PCa) has not been confirmed. However, these two entities share multiple risk factors like chronic inflammation, metabolic disorders, and androgen-dependent growth. Therefore, an association at a molecular level is at least possible, if not likely. We sought to identify variations in gene expression that could help elucidate some of the pathways for development of PCa in patients with BPH. METHODS: We included 98 men with BPH, positive prostate MRI (PIRADS ≥4), and subsequent negative targeted biopsy from 11/2014 – 01/2018. RNA sequencing was performed on tissue cores from the MRI lesion, as well as cores from a distant region (n=2 biopsy regions per patient). All patients were followed for at least 3 years to identify those who went on to develop PCa. We compared the genetic profiles of those who did not develop PCa (“BPH-only”) vs. those who did (“BPH/PCa”). Then, we identified the subset of men with BPH who had the highest AUA symptom scores (AUAss) and compared their gene expression to the group with PCa. RESULTS: At a median follow up of 47.5 months, 83 men had no evidence of cancer and 15 had BPH/PCa. We compared gene expressions of 14 men with symptomatic BPH (AUAss ≥18) vs. 15 with BPH/PCa. There were two clusters of genes, suggesting the two groups had distinctive molecular features. Differential analysis revealed genes that were upregulated in BPH-only and downregulated in BPH/PCa, and vice versa (Figure 1). Symptomatic BPH men had upregulation of T-cell activation markers (TCR-CD3, PKC theta, ZAP70, LCK) and chemokine receptor expression. In contrast, men with BPH/PCa had upregulation of NKX3-1 and HOXB13 transcription factors associated with luminal epithelial progenitors, but depleted of immune cells, suggesting a cell-autonomous role in immune evasion. CONCLUSIONS: Symptomatic BPH with immune-enriched landscapes may support anti-tumor immunity. Furthermore, RNA sequencing of benign biopsy tissue showing upregulation of NKX3-1 and HOXB13 with absence of T-cells, might help identifying men who are at higher risk of developing PCa, which could help tailoring their treatment and potentially prevent the development of PCa. Source of Funding: Midwest Stone Institute © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e790 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Nimrod Barashi Gozal More articles by this author Tiandao Li More articles by this author Bo Zhang More articles by this author Charles Nottingham More articles by this author Gerald Andriole More articles by this author Kiran Mahajan More articles by this author Eric Kim More articles by this author Expand All Advertisement PDF DownloadLoading ...