Abstract PR013: Comprehensive spatial profiling of prostate cancer metastasis: Mapping clonal evolution, microenvironment dynamics, and early metastatic markers

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Abstract The progression of prostate cancer (PCa) to metastatic disease remains a critical clinical challenge, making it essential to gain a detailed understanding of the factors that enable certain subclones to invade and spread. Building on our previous study, which examined genomic variations in benign and malignant prostate tissues by inferring copy number alterations (CNA) from spatial transcriptomics data1, this study aims to trace the spatial evolutionary trajectories of PCa subclones from the primary tumor to matched lymph node metastases and to identify alterations in associated microenvironments and early diagnostic markers. To achieve this, we performed spatial transcriptomics on entire prostate axial disks and patient-matched lymph node metastases from 10 individuals. Standard spatial transcriptomics (55 µm) was used for tissue profiling; from the spatial transcriptomics data, copy number alterations (CNAs) were inferred to identify distinct tumor subclones, and a clone-tree was constructed to describe their evolutionary relationships. Additionally, a high-resolution spatial transcriptomics (2 µm) technology was employed to gain a cellular-level view of the immediate tumor-microenvironment (TME) surrounding specific subclones. Analysis of over 1,000,000 barcoded regions identified many distinct tumor subclones, enabling us to trace their evolutionary trajectories spatially. We observed notable subclonal events within the lymph nodes, including polyclonal colonization, indicating multiple dissemination events during the evolution of the primary disease. Exploration of the immediate TME revealed significant cellular heterogeneity and upregulation of genes related to antigen presentation and inflammatory pathways concentrated near ancestral tumor clones, specifically at the tumor border. By focusing on the inferred CNA profiles of the metastasizing clone across patients, we identified several common features. Additionally, we were able to identify potential lethal disease as early as the diagnostic core needle biopsy stage by detecting features of metastasis and pinpointing the metastasizing clone. In summary, our study provides a detailed spatial map of PCa clonal evolution and dissemination, linking primary tumors to nodal metastases and revealing altered cell composition and gene expression around tumor clone borders. Importantly, it demonstrates subclonal events within lymph nodes, polyclonal colonization, and the potential to identify metastasizing clones as early as the diagnostic phase, which holds strong implications for precision oncology and early intervention. 1. Erickson, A., He, M., Berglund, E. et al. Spatially resolved clonal copy number alterations in benign and malignant tissue. Nature 608, 360–367 (2022). https://doi.org/10.1038/s41586-022-05023-2 Citation Format: Mengxiao He, Sandy Figiel, Max Beesley, Jintong Shi, Wencheng Yin, Emmanouela Perisynaki, Richard Colling, Ian G. Mills, Joakim Lundeberg, Alastair D. Lamb. Comprehensive spatial profiling of prostate cancer metastasis: Mapping clonal evolution, microenvironment dynamics, and early metastatic markers [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Innovations in Prostate Cancer Research and Treatment; 2026 Jan 20-22; Philadelphia PA. Philadelphia (PA): AACR; Cancer Res 2026;86(2_Suppl):Abstract nr PR013.

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