Dudka Ilona, Figueira João, Wikström Pernilla, Bergh Anders, Gröbner Gerhard
Department of Chemistry, Umeå University, Umeå, Sweden.
Department of Medical Biosciences, Pathology, Umeå University, Umeå, Sweden.
Front Mol Biosci. 2025 Apr 7;12:1426949. doi: 10.3389/fmolb.2025.1426949. eCollection 2025.
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 displaying the adaptive responses in benign tissues near tumors.
Here, we applied high-resolution magic angle spinning nuclear magnetic resonance (HR MAS NMR) to identify metabolomic biomarkers of possible diagnostic value in benign prostate tissues near low/high-grade tumors.
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 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 were 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) 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.
前列腺癌（PC）的诊断依赖于前列腺活检的组织病理学检查，而这种检查受到所有存在肿瘤的取样不足的限制。纳入来自非前列腺癌但受肿瘤影响的正常组织（TINT）的样本，可能通过展示肿瘤附近良性组织中的适应性反应来提高诊断能力。
在此，我们应用高分辨率魔角旋转核磁共振（HR MAS NMR）来识别低/高级别肿瘤附近良性前列腺组织中可能具有诊断价值的代谢生物标志物。
与低级别肿瘤（B ISUP 1 + 2）附近的良性样本相比，高级别肿瘤（B ISUP 3 + 4）附近的良性样本表现出代谢谱的改变。两组之间六种代谢物的水平有所不同；与低级别肿瘤（B ISUP 1 + 2）附近的良性样本相比，高级别肿瘤（B ISUP 3 + 4）附近的良性样本中肌醇、赖氨酸、丝氨酸以及赖氨酸/亮氨酸/精氨酸的组合信号增加，而乙醇胺和乳酸水平降低。此外，我们揭示了非癌组织中代谢差异与其到最近肿瘤的距离的函数关系。与距离较远（d≥1 cm）的良性组织相比，距离肿瘤较近（d≤5 mm）的良性组织中有八种代谢物（谷胱甘肽、谷氨酸、谷氨酸/谷氨酰胺的组合信号 - glx、甘油、肌苷、乙醇胺、丝氨酸和精氨酸）存在差异。
我们基于HR MAS NMR的方法在前列腺活检中识别出了代谢特征，这些特征反映了同一前列腺中良性组织对附近肿瘤存在的反应，并证实了TINT概念在改善前列腺癌诊断和理解肿瘤 - 组织相互作用方面的作用。
