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Spatial multi-omics identifies aggressive prostate cancer signatures highlighting pro-inflammatory chemokine activity in the tumor microenvironment

Author

Listed:
  • Sebastian Krossa

    (Norwegian University of Science and Technology, Department of Circulation and Medical Imaging
    St. Olavs Hospital HF, Central Staff)

  • Maria K. Andersen

    (Norwegian University of Science and Technology, Department of Circulation and Medical Imaging
    Trondheim University Hospital, Clinic of Surgery, St. Olavs Hospital)

  • Elise M. Sandholm

    (Norwegian University of Science and Technology, Department of Circulation and Medical Imaging
    Trondheim University Hospital, Clinic of Surgery, St. Olavs Hospital)

  • Maximilian Wess

    (Norwegian University of Science and Technology, Department of Circulation and Medical Imaging)

  • Antti Kiviaho

    (Tampere University and TAYS Cancer Center, Prostate Cancer Research Center, Faculty of Medicine and Health Technology)

  • Abhibhav Sharma

    (Norwegian University of Science and Technology, Department of Circulation and Medical Imaging
    Norwegian University of Science and Technology (NTNU), HUNT Center for Molecular and Clinical Epidemiology, Department of Public Health and Nursing)

  • Sini Hakkola

    (Tampere University and TAYS Cancer Center, Prostate Cancer Research Center, Faculty of Medicine and Health Technology)

  • Yangyang Hao

    (Veracyte)

  • Mohammed Alshalalfa

    (Veracyte)

  • Elai Davicioni

    (Veracyte)

  • Trond Viset

    (Trondheim University Hospital, Department of Pathology, St. Olavs Hospital)

  • Øystein Størkersen

    (Trondheim University Hospital, Department of Pathology, St. Olavs Hospital)

  • R. Jeffrey Karnes

    (Mayo Clinic, Department of Urology)

  • Daniel E. Spratt

    (Case Western Reserve University, UH Seidman Cancer Center)

  • Guro F. Giskeødegård

    (Norwegian University of Science and Technology (NTNU), HUNT Center for Molecular and Clinical Epidemiology, Department of Public Health and Nursing)

  • Matti Nykter

    (Tampere University and TAYS Cancer Center, Prostate Cancer Research Center, Faculty of Medicine and Health Technology
    Foundation for the Finnish Cancer Institute)

  • Morten B. Rye

    (Trondheim University Hospital, Clinic of Surgery, St. Olavs Hospital
    Norwegian University of Science and Technology, Department of Clinical and Molecular Medicine)

  • Alfonso Urbanucci

    (Tampere University and TAYS Cancer Center, Prostate Cancer Research Center, Faculty of Medicine and Health Technology
    Oslo University Hospital, Department of Tumor Biology, Institute for Cancer Research)

  • May-Britt Tessem

    (Norwegian University of Science and Technology, Department of Circulation and Medical Imaging
    Trondheim University Hospital, Clinic of Surgery, St. Olavs Hospital)

Abstract

Understanding the characteristics of the tumor microenvironment (TME) associated with aggressive prostate cancer (PCa) is essential for accurate diagnosis and treatment. We interrogated spatially resolved multi-omics data to find molecular stratifiers of aggressive PCa. We report an aggressive prostate cancer (APC) gene expression signature predictive of increased risk of relapse and metastasis in a cohort of 1,588 patients. Further, we present a chemokine-enriched-gland (CEG) signature specific to non-cancerous prostatic glands from patients with aggressive cancer. The CEG signature is characterized by upregulated expression of pro-inflammatory chemokines, club-like cell enrichment, and immune cell infiltration of surrounding stroma. The activity of both signatures is correlated with reduced citrate and zinc levels and loss of normal prostate secretory gland functions. In summary we report that an increased inflammatory status linked to chemokine production, club-like cell enrichment, and metabolic changes in normal-appearing prostatic glands is associated with the subsequent development of aggressive PCa.

Suggested Citation

  • Sebastian Krossa & Maria K. Andersen & Elise M. Sandholm & Maximilian Wess & Antti Kiviaho & Abhibhav Sharma & Sini Hakkola & Yangyang Hao & Mohammed Alshalalfa & Elai Davicioni & Trond Viset & Øystei, 2025. "Spatial multi-omics identifies aggressive prostate cancer signatures highlighting pro-inflammatory chemokine activity in the tumor microenvironment," Nature Communications, Nature, vol. 16(1), pages 1-21, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-65161-9
    DOI: 10.1038/s41467-025-65161-9
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    References listed on IDEAS

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