Pd09-06 Exploring Stromal Dynamics in Prostate Cancer: Insights From Spatial Transcriptomic Analyses

You have accessJournal of UrologyProstate Cancer: Basic Research & Pathophysiology II (PD09)1 May 2024PD09-06 EXPLORING STROMAL DYNAMICS IN PROSTATE CANCER: INSIGHTS FROM SPATIAL TRANSCRIPTOMIC ANALYSES Sandy Figiel, Wencheng Yin, Mengxiao He, Renuka Teague, Thineskrishna Anbarasan, Nithesh Ranasinha, Sophia Abusamra, Reema Singh, Dimitrios Doultsinos, Ninu Poulose, Andrew Erickson, Clare Verrill, Richard Colling, Pelvender Gill, Richard J. Bryant, Olivier Cussenot, Massimo Loda, Freddie C. Hamdy, Dan J. Woodcock, Ian G. Mills, Joakim Lundeberg, Solna Sweden, and Alastair D. Lamb Sandy FigielSandy Figiel , Wencheng YinWencheng Yin , Mengxiao HeMengxiao He , Renuka TeagueRenuka Teague , Thineskrishna AnbarasanThineskrishna Anbarasan , Nithesh RanasinhaNithesh Ranasinha , Sophia AbusamraSophia Abusamra , Reema SinghReema Singh , Dimitrios DoultsinosDimitrios Doultsinos , Ninu PouloseNinu Poulose , Andrew EricksonAndrew Erickson , Clare VerrillClare Verrill , Richard CollingRichard Colling , Pelvender GillPelvender Gill , Richard J. BryantRichard J. Bryant , Olivier CussenotOlivier Cussenot , Massimo LodaMassimo Loda , Freddie C. HamdyFreddie C. Hamdy , Dan J. WoodcockDan J. Woodcock , Ian G. MillsIan G. Mills , Joakim LundebergJoakim Lundeberg , Solna SwedenSolna Sweden , and Alastair D. LambAlastair D. Lamb View All Author Informationhttps://doi.org/10.1097/01.JU.0001008572.33286.63.06AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Prostate cancer's prognosis varies widely, from indolent to aggressive forms causing metastasis and death. The lack of reliable diagnostic tools and effective treatments poses substantial challenges in its management and research. Understanding the mechanisms driving prostate cancer's diversity is crucial for improved treatment. Spatial genomics has allowed us to define clonal heterogeneity, revealing insights into the cancer's origin and emphasising the stroma's role in tumour development, fostering growth and immune evasion. This study explores the stroma in primary and metastatic prostate cancer tissue, aiming to identify transformation-promoting factors. METHODS: We conducted spatial transcriptomic analyses (Visium v2) on FFPE tissues from primary and nodal metastatic tissues. We analysed expression data using spatial inferred copy number variations and constructed a phylogenetic tree to describe clonal events in tumour regions (https://github.com/aerickso/SpatialInferCNV). We performed differential gene expression analyses of stromal cells around each tumour clone, employing combined cellular deconvolution. RESULTS: We found significant variations within stromal cells around distinct tumour clones. Interestingly, we found upregulation of genes associated with antigen presentation and inflammatory response pathways in the stroma surrounding ancestor tumour clones that had not yet acquired metastatic potential. For example, gene CD74 was highly expressed in the stroma around ancestor clone (clone B) compared to descendant clone (clone C) in the apex of the prostate. We also observed this discrepancy in the base, where we identified a lethal clone that had spread to the lymph nodes. Indeed, the stroma around the ancestor clone (clone C1) is enriched in IGHA1, compared to the stroma around the lethal clone (clone X1). CONCLUSIONS: Our study reveals altered stromal gene expression surrounding different tumour clones, highlighting the dynamic interplay between cancer cells and their microenvironment. This distinctive stromal profile offers mechanistic insights underpinning phenotypic variability. It raises the possibility of using the stroma as a window to differentiate tumour lethality from indolent disease, as well as offering targets for personalised treatment strategies. Download PPT Source of Funding: The present work was supported by Cancer Research UK (CRUK), Hanson Trust Research, the John Black Charitable Foundation, Prostate Cancer Foundation, NIHR Oxford Biomedical Research Centre, European Research Council, Swedish Society for Cancer Research © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e181 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Sandy Figiel More articles by this author Wencheng Yin More articles by this author Mengxiao He More articles by this author Renuka Teague More articles by this author Thineskrishna Anbarasan More articles by this author Nithesh Ranasinha More articles by this author Sophia Abusamra More articles by this author Reema Singh More articles by this author Dimitrios Doultsinos More articles by this author Ninu Poulose More articles by this author Andrew Erickson More articles by this author Clare Verrill More articles by this author Richard Colling More articles by this author Pelvender Gill More articles by this author Richard J. Bryant More articles by this author Olivier Cussenot More articles by this author Massimo Loda More articles by this author Freddie C. Hamdy More articles by this author Dan J. Woodcock More articles by this author Ian G. Mills More articles by this author Joakim Lundeberg More articles by this author Solna Sweden More articles by this author Alastair D. Lamb More articles by this author Expand All Advertisement PDF downloadLoading ...