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ORIGINAL RESEARCH article
Front. Mol. Biosci.
Sec. Metabolomics
Volume 12 - 2025 | doi: 10.3389/fmolb.2025.1426949
This article is part of the Research Topic Metabolomics in Personalized Cancer Medicine View all 6 articles
Metabolic readouts of tumor instructed normal tissues (TINT) identify aggressive prostate cancer subgroups for tailored therapy The metabolome of benign prostate tissues is influenced by nearby tumors of high grade
Provisionally accepted- 1 Department of Chemistry, Umeå University, Umeå, Sweden
- 2 Department of Medical Biosciences, Pathology, Umeå University, Umeå, Sweden
Introduction: Prostate cancer (PC) diagnosis relies on histopathological examination of prostate biopsies, which is restricted by insufficient sampling of all tumors present. Including samples from non-PC but tumor instructed normal tissues (TINT) may increase the diagnostic power by exploring the adaptive responses in benign tissues near tumors.Methods: Here, we applied high-resolution magic angle spinning nuclear magnetic resonance (HR MAS NMR) to identify metabolomic biomarkers with high of possible diagnostic value in benign prostate tissues near low/high-grade tumors.Results: Benign samples near high-grade tumors (B ISUP 3+4) exhibited altered metabolic profiles compared to those close to low-grade tumors (B ISUP 1+2). The levels of six metabolites were significantly differentiated between the two groups; myo-inositol, lysine, serine and combined signal of lysine/leucine/arginine were increased in benign samples near high-grade tumors (B ISUP 3+4) compared to near low-grade tumors (B ISUP 1+2), while levels of ethanolamine and lactate decreased. Additionally, we revealed metabolic differences in non-cancer tissues as a function of their distance to the nearest tumor. Eight metabolites (glutathione, glutamate, combined signal of glutamate/glutamine -glx, glycerol, inosine, ethanolamine, serine and arginine) significantly differentiated between benign tissue located close to the tumor (d ≤ 5 mm) compared to those far away (d ≥ 1 cm).Our HR MAS NMR-based approach identified metabolic signatures in prostate biopsies that reflect the response of benign tissues to the presence of nearby located tumors in the same prostate and confirmed the power of the TINT concept for improved PC diagnostics and understanding of tumor-tissue interactions.
Keywords: Metabolomics, prostate cancer, TINT -tumor instructed normal tissue, HR MAS NMR, biomarker
Received: 02 May 2024; Accepted: 07 Mar 2025.
Copyright: © 2025 Dudka, Wikström, Bergh and Gröbner. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Anders Bergh, Department of Medical Biosciences, Pathology, Umeå University, Umeå, Sweden
Gerhard Gröbner, Department of Chemistry, Umeå University, Umeå, Sweden
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