Pd09-02 a Genetic Landscape of De Novo Neuroendocrine Prostate Cancer and Possible Novel Therapeutic Strategies Unveiled by Spatial Gene Expression Analysis

You have accessJournal of UrologyProstate Cancer: Basic Research & Pathophysiology II (PD09)1 May 2024PD09-02 A GENETIC LANDSCAPE OF DE NOVO NEUROENDOCRINE PROSTATE CANCER AND POSSIBLE NOVEL THERAPEUTIC STRATEGIES UNVEILED BY SPATIAL GENE EXPRESSION ANALYSIS Ryuta Watanabe, Noriyoshi Miura, Mie Kurata, Riko Kitazawa, Tadahiko Kikugawa, and Takashi Saika Ryuta WatanabeRyuta Watanabe , Noriyoshi MiuraNoriyoshi Miura , Mie KurataMie Kurata , Riko KitazawaRiko Kitazawa , Tadahiko KikugawaTadahiko Kikugawa , and Takashi SaikaTakashi Saika View All Author Informationhttps://doi.org/10.1097/01.JU.0001008572.33286.63.02AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Introduction and objectives: Neuroendocrine prostate cancer (NEPC) constitutes less than 1% of all prostate malignancies and displays a notably worse prognosis when compared to the conventional androgen receptor-positive prostate adenocarcinoma (ARPC). Rare instances exist where both de novo NEPC and ARPC are diagnosed concurrently within the same tissue specimen. Our study focuses on an exceptional case of a 78-year-old male patient treated at Ehime University Hospital, who was diagnosed with ARPC as well as adjacent de novo metastatic NEPC. This case serves as an ideal subject for gene expression analysis comparing de novo NEPC with ARPC. METHODS: Methods: We employed Visium CytAssist Spatial Gene Expression technology from 10x Genomics on formalin-fixed, paraffin-embedded (FFPE) tissue samples from this unique case. RESULTS: Results: We found elevated expression levels of neuroendocrine markers like PEG10, DLL3, NCAM1, SYP, and CHGA in de novo NEPC regions. Androgen receptor markers such as KLK3, ACPP, TMPRSS2, and NKX3.1 were elevated in ARPC regions. Additionally, genes like Chek1, BRCA1/2, TOP2A, and FANCA were also elevated in NEPC areas, pointing towards the potential efficacy of PARP and TOP2 inhibitors. On the other hand, Rbfox3 and SFRTM2 expression levels were suppressed in the NEPC tumor microenvironment, hinting at links to epithelial-mesenchymal transition (EMT) and Wnt pathways. Moreover, fibrotic markers including HGF, HMOX1, ELN, and GREM1 were elevated, suggesting that de novo NEPC tumors are more 'immune cold,' emphasizing the need for therapies that boost the effectiveness of immune checkpoint inhibitors. CONCLUSIONS: Conclusions: The collection of further case studies and foundational data may pave the way for the formulation of innovative treatments for NEPC and enhance survival rates for individuals with castration-resistant prostate cancer. Our study represents one of the pioneering works employing CytAssist Visium on FFPE samples and is the inaugural effort to explore gene expression in coexisting ARPC and de novo NEPC. A portion of this study's findings has been published in the International Journal of Molecular Science (IJMS) in May 2023. Download PPT Source of Funding: JSPS KAKENHI, grant number 22K09449JSPS KAKENHI, grant number 22KK0135 KOWA LIFE SCIENCE FOUNDATIONThe Japanese Foundation for Prostate ResearchSGH FOUNDATION LIFE SCIENCE FOUNDATION OF JAPAN © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e179 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Ryuta Watanabe More articles by this author Noriyoshi Miura More articles by this author Mie Kurata More articles by this author Riko Kitazawa More articles by this author Tadahiko Kikugawa More articles by this author Takashi Saika More articles by this author Expand All Advertisement PDF downloadLoading ...