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

Sebastian Krossa (), Maria K. Andersen, Elise M. Sandholm, Maximilian Wess, Antti Kiviaho, Abhibhav Sharma, Sini Hakkola, Yangyang Hao, Mohammed Alshalalfa, Elai Davicioni, Trond Viset, Øystein Størkersen, R. Jeffrey Karnes, Daniel E. Spratt, Guro F. Giskeødegård, Matti Nykter, Morten B. Rye, Alfonso Urbanucci and May-Britt Tessem ()
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Sebastian Krossa: Norwegian University of Science and Technology, Department of Circulation and Medical Imaging
Maria K. Andersen: Norwegian University of Science and Technology, Department of Circulation and Medical Imaging
Elise M. Sandholm: Norwegian University of Science and Technology, Department of Circulation and Medical Imaging
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
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
Morten B. Rye: Trondheim University Hospital, Clinic of Surgery, St. Olavs Hospital
Alfonso Urbanucci: Tampere University and TAYS Cancer Center, Prostate Cancer Research Center, Faculty of Medicine and Health Technology
May-Britt Tessem: Norwegian University of Science and Technology, Department of Circulation and Medical Imaging

Nature Communications, 2025, vol. 16, issue 1, 1-21

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41467-025-65161-9

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