Karpiuk Kacper Robert, Młynarczyk Grzegorz, Matowicka-Karna Joanna, Darewicz Barbara
Department of Urology, Medical University of Białystok, 15-276 Białystok, Poland.
Department of Clinical Laboratory Diagnostics, Medical University of Bialystok, 15-269 Białystok, Poland.
Int J Mol Sci. 2025 Sep 18;26(18):9130. doi: 10.3390/ijms26189130.
The interaction between tumor cells and stroma in urological malignancies is governed by secreted and damage-associated factors that promote angiogenesis, immune modulation, and metastasis. This review synthesizes current evidence on six biomarkers-GDF15, VEGF, TGF-1, HSP90, HMGB1, and S100A9-detailing their biological functions and clinical implications. We discuss GDF15's roles in metabolic stress and immune regulation, VEGF's central role in neovascularization, and TGF-1's dualistic tumor-suppressive and promotive effects. We then examine damage-associated molecular patterns, highlighting HSP90's extracellular immunomodulation, HMGB1's signaling via pattern-recognition receptors, and S100A9's pro-inflammatory activity through RAGE and Toll-like receptors. Comparative analyses across renal cell carcinoma and bladder cancer cohorts elucidate each marker's diagnostic accuracy, prognostic value, and predictive capacity for targeted therapies. Notably, GDF15 and HSP90 correlate with ferroptosis susceptibility in RCC and urinary VEGF with HMGB1 increases the chances of non-invasive bladder cancer detection. We suggest that multiplexed biomarker panels could enhance early detection, risk stratification, and personalized treatment in urological oncology. We advocate for prospective studies to validate thresholds, clarify interactions, and improve clinical integration.
泌尿系统恶性肿瘤中肿瘤细胞与基质之间的相互作用受分泌因子和损伤相关因子的调控，这些因子可促进血管生成、免疫调节和转移。本综述综合了关于六种生物标志物——生长分化因子15（GDF15）、血管内皮生长因子（VEGF）、转化生长因子-β1（TGF-β1）、热休克蛋白90（HSP90）、高迁移率族蛋白B1（HMGB1）和S100钙结合蛋白A9（S100A9）的现有证据，详细阐述了它们的生物学功能和临床意义。我们讨论了GDF15在代谢应激和免疫调节中的作用、VEGF在新生血管形成中的核心作用以及TGF-β1的双重肿瘤抑制和促进作用。然后，我们研究损伤相关分子模式，重点介绍HSP90的细胞外免疫调节、HMGB1通过模式识别受体的信号传导以及S100A9通过晚期糖基化终末产物受体（RAGE）和Toll样受体的促炎活性。对肾细胞癌和膀胱癌队列的比较分析阐明了每种标志物的诊断准确性、预后价值和靶向治疗的预测能力。值得注意的是，GDF15和HSP90与肾细胞癌中的铁死亡易感性相关，尿液VEGF与HMGB1增加了非侵袭性膀胱癌检测的机会。我们认为，多重生物标志物组合可以提高泌尿系统肿瘤学中的早期检测、风险分层和个性化治疗水平。我们主张进行前瞻性研究，以验证阈值、阐明相互作用并改善临床整合。
