Zhao Liping, Xu Zhe, Ren Lingyun, Zheng Sufen, Gao Jingyu, Che Hang, Zhang Aimin
Department of Gastroenterology, The Third Hospital of Shijiazhuang, Shijiazhuang, China.
Department of Urology, The First Hospital of Hebei Medical University, No. 89 Donggang Road, Yuhua District, Shijiazhuang, 050000, China.
Sci Rep. 2025 Sep 1;15(1):32197. doi: 10.1038/s41598-025-12187-0.
This study aimed to investigate the relationship between peripheral blood transferrin receptor protein (TfR) and tumor cell ferroptosis, as well as bladder cancer invasion and metastasis, and further reveal the mechanism of action of TfR in bladder cancer progression. Fifteen patients with bladder cancer, treated at the Department of Urology in our hospital from February 2022 to August 2023, were recruited as research subjects. The patients were aged between 44 and 68 years, with an average age of 52.57 ± 4.38 years. General patient data were analyzed, and the level of peripheral blood TfR was detected at baseline (T0), 3 months (T1), 6 months (T2), and 9 months (T3) post-treatment using a repeated measures design. The levels of GPX4, Ferroportin, and transferrin receptor in the peripheral blood were measured by enzyme-linked immunosorbent assay (ELISA) at T0, T1, T2, and T3. Tumor size and invasiveness were assessed using MRI imaging at the same time points. Protein expressions of MMP-2, MMP-9, and N-Cadherin were analyzed by Western blot at T0, T1, T2, and T3. Pearson correlation analysis was utilized to examine the relationship between TfR, GPX4, Ferroportin, transferrin receptor levels, and tumor invasion and metastasis. As treatment progressed, TfR levels at T3 and T2 were significantly lower than those at T1 and T0 (P < 0.05). Similarly, markers of tumor cell ferroptosis (GPX4, Ferroportin, and transferrin receptor) also showed significant decreases (P < 0.05). Tumor volume at T3 was smaller compared to T0, T1, and T2 (P < 0.05). The protein expressions of MMP-2, MMP-9, and N-Cadherin at T3 and T2 were significantly lower than those at T0 and T1 (P < 0.05). Increased peripheral blood TfR levels and reduced tumor cell ferroptosis were associated with higher cancer cell invasion and metastasis. A reduction in peripheral blood TfR levels is associated with the effectiveness of bladder cancer treatment. This reduction may decrease the invasiveness and migration ability of cancer cells by affecting the iron metabolism pathway. These findings may provide a basis for the development of new targeted therapeutic strategies to improve outcomes for patients with bladder cancer.
本研究旨在探讨外周血转铁蛋白受体蛋白（TfR）与肿瘤细胞铁死亡以及膀胱癌侵袭和转移之间的关系，并进一步揭示TfR在膀胱癌进展中的作用机制。选取2022年2月至2023年8月在我院泌尿外科接受治疗的15例膀胱癌患者作为研究对象。患者年龄在44至68岁之间，平均年龄为52.57±4.38岁。分析患者的一般资料，并采用重复测量设计在治疗前基线（T0）、治疗后3个月（T1）、6个月（T2）和9个月（T3）检测外周血TfR水平。在T0、T1、T2和T3时，采用酶联免疫吸附测定（ELISA）法检测外周血中谷胱甘肽过氧化物酶4（GPX4）、铁转运蛋白和转铁蛋白受体的水平。在相同时间点使用磁共振成像（MRI）评估肿瘤大小和侵袭性。在T0、T1、T2和T3时，通过蛋白质免疫印迹法分析基质金属蛋白酶2（MMP-2）、基质金属蛋白酶9（MMP-9）和N-钙黏蛋白的蛋白表达。采用Pearson相关性分析来检验TfR、GPX4、铁转运蛋白、转铁蛋白受体水平与肿瘤侵袭和转移之间的关系。随着治疗的进行，T3和T2时的TfR水平显著低于T1和T0时（P<0.05）。同样，肿瘤细胞铁死亡标志物（GPX4、铁转运蛋白和转铁蛋白受体）也显著降低（P<0.05）。与T0、T1和T2相比，T3时的肿瘤体积较小（P<0.05）。T3和T2时MMP-2、MMP-9和N-钙黏蛋白的蛋白表达显著低于T0和T1时（P<0.05）。外周血TfR水平升高和肿瘤细胞铁死亡减少与癌细胞更高的侵袭和转移相关。外周血TfR水平降低与膀胱癌治疗效果相关。这种降低可能通过影响铁代谢途径降低癌细胞的侵袭和迁移能力。这些发现可能为开发新的靶向治疗策略以改善膀胱癌患者的预后提供依据。
