PD04-06 IDENTIFYING NOVEL REGULATORS OF MACROPHAGE TUMOR CELL METABOLIC INTERACTIONS IN PROSTATE CANCER

Abstract

You have accessJournal of UrologyCME1 Apr 2023PD04-06 IDENTIFYING NOVEL REGULATORS OF MACROPHAGE TUMOR CELL METABOLIC INTERACTIONS IN PROSTATE CANCER Asmaa Elkenawi, Ryan Putney, Amparo Serna, Jasreman Dhillon, and Kosj Yamoah Asmaa ElkenawiAsmaa Elkenawi More articles by this author , Ryan PutneyRyan Putney More articles by this author , Amparo SernaAmparo Serna More articles by this author , Jasreman DhillonJasreman Dhillon More articles by this author , and Kosj YamoahKosj Yamoah More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003228.06AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: African American men (AA) are more than twice as likely to die of prostate cancer (PCa) compared to European American men (EA). Among many contributing factors, unraveling the metabolic derangements in PCa of AA holds a promise in reducing health disparity. METHODS: We examined publicly available prostate cancer datasets for race dependent differential gene expression. We prospectively examined the differential gene expression of PCa from clinically matched AA and EA in the VANDAAM clinical trial. The VANDAAM study is a validation study of DecipherTM genomic testing in 240 men with localized PCa. We combined computational and experimental approaches to explore the molecular mechanisms of top candidate genes including these involved in metabolism. We then developed a novel metabolomic workflow that profiles patient- specific nutrient consumption to predict anti-cancer efficacy and validate novel biomarkers. RESULTS: We identified aminopeptidase N (ANPEP) as one of the top candidate genes to be overexpressed in AA. Aminopeptidase N is involved in endocytosis, cholesterol and amino acid transport and peptide hydrolysis. Unbiased computational analyses of the VANDAAM revealed that ANPEP correlates with signatures of cholesterol transport, estrogen and androgen receptor (AR) signaling. Based on our recent study demonstrating dominance of these signatures in macrophage rich PCa, we reasoned that ANPEP expression may be driven in part by high macrophage infiltration in AA. Thus, we compared immune cell repertoire in patients with high ANPEP and low ANPEP by deconvoluting immune cell content using the in silico approach, CIBERSORT. These analyses illustrated that only AA patients with high ANPEP expression significantly accumulated high content of M1 inflammatory macrophages. Immune phenotyping of prostate tumors demonstrated that ANPEP indeed represents a marker of M1 inflammatory macrophages. To unravel role of ANPEP in regulating cholesterol and amino acid transport, we developed a Liquid chromatography-high resolution mass spectrometry (LC-HRMS) -based approach to measure cholesterol and amino acids in explants derived from AA and EA prostate cancer patients. This innovative approach enables us to perform mechanistic studies by determining metabolic dependency on specific amino acids as a function ANPEP or macrophage infiltration. CONCLUSIONS: ANPEP represents a macrophage related protein in PCa with a potential role in cholesterol, amino acid transport and / or androgen signaling. Source of Funding: Prostate Cancer Foundation (AE), Urology Care Foundation (AE), Prostate Cancer Foundation (KY) and Department of Defense award CDMRP-PC181013 (KY) © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e144 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Asmaa Elkenawi More articles by this author Ryan Putney More articles by this author Amparo Serna More articles by this author Jasreman Dhillon More articles by this author Kosj Yamoah More articles by this author Expand All Advertisement PDF downloadLoading ...