Pd09-11 Spatial Transcriptome Analysis Reveals the Tumor Heterogeneity and Niche Factors in Progressive Prostate Cancer

You have accessJournal of UrologyProstate Cancer: Basic Research & Pathophysiology II (PD09)1 May 2024PD09-11 SPATIAL TRANSCRIPTOME ANALYSIS REVEALS THE TUMOR HETEROGENEITY AND NICHE FACTORS IN PROGRESSIVE PROSTATE CANCER Yuto Baba, Takeo Kosaka, Yota Yasumizu, Hiroshi Hongo, Toshikazu Takeda, Kazuhiro Matsumoto, Hiroshi Nishihara, Yutaka Suzuki, and Mototsugu Oya Yuto BabaYuto Baba , Takeo KosakaTakeo Kosaka , Yota YasumizuYota Yasumizu , Hiroshi HongoHiroshi Hongo , Toshikazu TakedaToshikazu Takeda , Kazuhiro MatsumotoKazuhiro Matsumoto , Hiroshi NishiharaHiroshi Nishihara , Yutaka SuzukiYutaka Suzuki , and Mototsugu OyaMototsugu Oya View All Author Informationhttps://doi.org/10.1097/01.JU.0001008572.33286.63.11AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: It has been well-documented that expression patterns of androgen receptor (AR) and prostate-specific antigen (PSA) are changes within prostate cancer as the cancer evolves. However, the precise molecular functions and cell-cell interactions underpinning AR-indifferent or AR-null cancer lesions remain unclear. We investigated the intra-tumoral heterogeneity of aggressive prostate cancers and identify the specific niche factors responsible for maintaining tumor microenvironment through spatial transcriptomic analyses. METHODS: We conducted spatial transcriptome analyses on 15 specimens obtained from metastatic CRPC patients. Ligand-receptor (L-R) analyses were performed on the data to identify all potential ligand-receptor pairs and assess the strength of their interactions within specific regions of the tumor by using Seurat, an R package. From this analysis we identified important ligands, which were subsequently validated in patient-derived prostate cancer organoid models originating from the same individuals whose tissues were subjected to spatial transcriptomics. RESULTS: Spatial transcriptomic profiling effectively delineated tumor lesions based on AR and PSA expression. L-R analyses showed that in the lesions of conventional adenocarcinoma where both AR and PSA expression are maintained, are abundant with 136 L-R pairs on average including Wnt, TGF-beta, BMP, IGF, FGF signaling pathways. On the other hand, in the AR-indifferent lesions where only AR expressions are postive and double-negative tumor lesions, the L-R pairs are reduced to 96 and 6 signaling, respectively, suggesting that more dedifferentiated tumor lesions required fewer niche factors for their maintenance. Remarkably, we identified HBRG2 and MKD1 as the most commonly preserved niche molecules. Cell proliferation assays using the organoids demonstrated that these molecules accelerated growth, underscoring their pivotal roles in sustaining the microenvironment of the most malignant phenotype. Consequently, these molecules hold promise as potential therapeutic targets. CONCLUSIONS: Spatial transcriptome analysis unveiled crucial niche factors that play a significant role in sustaining the highly aggressive phenotype of prostate cancer. We further confirmed their impact on promoting cancer cell growth using patient-derived prostate cancer organoids. Source of Funding: No funding was received to assist with the presentation © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e183 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Yuto Baba More articles by this author Takeo Kosaka More articles by this author Yota Yasumizu More articles by this author Hiroshi Hongo More articles by this author Toshikazu Takeda More articles by this author Kazuhiro Matsumoto More articles by this author Hiroshi Nishihara More articles by this author Yutaka Suzuki More articles by this author Mototsugu Oya More articles by this author Expand All Advertisement PDF downloadLoading ...