Pd09-05 Differences in Genomic, Transcriptomic and Immune Landscape of Prostate Cancer (Pca) Based on Site of Metastasis (Mets)

You have accessJournal of UrologyProstate Cancer: Basic Research & Pathophysiology II (PD09)1 May 2024PD09-05 DIFFERENCES IN GENOMIC, TRANSCRIPTOMIC AND IMMUNE LANDSCAPE OF PROSTATE CANCER (PCA) BASED ON SITE OF METASTASIS (METS) Dhruv Puri, Umang Swami, Georges Gebrael, Shayan Nazari, Andrew Elliott, Chadi Nabhan, Rana R. Mckay, Emmanuel S. Antonarakis, Aditya Bagrodia, and Neeraj Agarwal Dhruv PuriDhruv Puri , Umang SwamiUmang Swami , Georges GebraelGeorges Gebrael , Shayan NazariShayan Nazari , Andrew ElliottAndrew Elliott , Chadi NabhanChadi Nabhan , Rana R. MckayRana R. Mckay , Emmanuel S. AntonarakisEmmanuel S. Antonarakis , Aditya BagrodiaAditya Bagrodia , and Neeraj AgarwalNeeraj Agarwal View All Author Informationhttps://doi.org/10.1097/01.JU.0001008572.33286.63.05AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: In patients with metastatic PCa, specific sites of metastasis are associated with differential survival, with lymph node (LN) only disease having the best survival, followed by bone, lung, and liver, each showing progressively worse survival. Herein, utilizing a large, multi-institutional, real-world dataset, we hypothesized that differences in molecular and immune landscape of PCa based on site of metastasis may explain different clinical outcomes. METHODS: DNA (592-gene panel or whole exome) and RNA (whole transcriptome) sequencing was performed for primary PCa (PPCa) and unpaired PCa mets sites (non-visceral: NV and visceral: V). Mismatch repair deficiency/microsatellite instability-high (dMMR/MSI-H) was tested by IHC/NGS, respectively. Tumor mutational burden (TMB) (high >10 mut/Mb) was assessed. Androgen receptor (AR) signaling score and Neuroendocrine Prostate Cancer (NEPC) score were calculated using previously defined RNA-based signatures. Statistical significance was determined by chi-square and Mann-Whitney U tests. RESULTS: 6074 PCa samples, including 3411 PPCa, 1634 NV (bone=784, LN=850) and 1029 V (liver: 468, lung: 177, bladder: 241, other: 143) were evaluated. Compared to PPCa, significantly higher mutation rates were observed for multiple genes in V (RB1, TP53, PTEN, CTNNB1, AR13, APC, and AKT1), and NV mets (AR, SPOP, TP53, CTNNB1, KMT2C) (p<0.05 for all). Alterations of RB1, APC and AR were more frequent, and SPOP less common in liver mets compared to PPCa, while SPOP, KRAS, PIK3CA, APC and BAP1 mutations were more common in lung mets (p<0.05 for all). Compared to PPCa, V and NV mets had higher AR signaling and interferon-γ scores, while V mets had higher NEPC scores and were more frequently PD-L1+ (SP142) and TMB-high (p<0.05 for all). No differences in dMMR/MSI-H was observed between PPCa, V and NV mets. AR-V7 variant prevalence was significantly higher in V (36%) and NV (33%) mets compared to PPCa (7%, p-value <0.05). CONCLUSIONS: This study highlights distinct molecular profiles in metastatic prostate cancer (PCa) based on metastasis site, underlining the importance of personalized treatment strategies. The findings, particularly the variations in gene mutations and AR signaling, are crucial in tailoring management approaches for advanced PCa. Download PPT Source of Funding: None © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e180 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Dhruv Puri More articles by this author Umang Swami More articles by this author Georges Gebrael More articles by this author Shayan Nazari More articles by this author Andrew Elliott More articles by this author Chadi Nabhan More articles by this author Rana R. Mckay More articles by this author Emmanuel S. Antonarakis More articles by this author Aditya Bagrodia More articles by this author Neeraj Agarwal More articles by this author Expand All Advertisement PDF downloadLoading ...