Abstract

Abstract In recent years, advances in spatial transcriptomics have revolutionized our understanding of the tumor microenvironment, providing crucial insights into the complex interplay of different cell types within cancer tissues. In this study, we employed the new, high definition Visium spatial transcriptomics assay (Visium HD) to investigate the intricate molecular landscape of prostate cancer at single-cell scale resolution and across the whole transcriptome. Our research focused on deciphering the spatial heterogeneity of gene expression patterns within the tumor microenvironment, shedding light on the interactions between cancer cells, stromal cells, and vasculature. The Visium HD assay enables an unbiased exploration of the transcriptome on FFPE tissue sections mounted on standard glass slides. Combining gene expression data with H&E images from the same section, it allows precise characterization of local molecular features and disease states at single-cell scale. We analyzed a set of human prostate adenocarcinoma samples with the Visium HD assay, and identified spatially regulated gene signatures associated with specific cell types and functional pathways. Our findings have recapitulated previously identified molecular markers, including VEGFA and MYC which have been implicated in tumor progression and angiogenesis. The spatial gene expression patterns had good correlation with histological annotations of cancerous and normal tissue within the H&E image. However, Visium HD allowed us to further observe molecular processes and pathways specific to this adenocarcinoma sample. This integrative approach offers valuable implications for personalized cancer therapy and the development of targeted interventions tailored to the spatial context of individual tumors. Our study underscores the significance of understanding the spatial organization of the whole transcriptome in cancer tissues, and highlights the potential of the Visium HD platform as a powerful tool for unraveling the complexities of the tumor microenvironment. These insights pave the way for the development of innovative therapeutic strategies and precision medicine approaches, ultimately contributing to improved outcomes for cancer patients. Citation Format: Yifeng Yin, Jerald Sapida, David Sukovich, David Patterson, Augusto Tentori. Unraveling spatial complexity of the tumor microenvironment: A whole transcriptomic perspective with Visium HD [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3645.

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