Journal Article

Investigating the relationship between peripheral blood transferrin receptor protein and tumor cell ferroptosis, invasion, and metastasis in bladder cancer

Ren, Lingyun, Xu, Zhe, Zheng, Sufen, Che, Hang, Gao, Jingyu, Zhang, Aimin, Zhao, Liping

2025

Overview

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.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 692/4025/1334 / 692/4028/67/589/1336 / Adult / Aged / Antigens, CD / Apoptosis / Bladder cancer / Blood levels / Cadherins - metabolism / Cancer therapies / Cation Transport Proteins - blood / Cell death / Cell growth / Cell migration / Chemotherapy / Correlation analysis / Creatinine / Enzyme-linked immunosorbent assay / Female / Females / Ferroportin / Ferroptosis / Gelatinase A / Gelatinase B / Glutathione / Humanities and Social Sciences / Humans / Immunotherapy / Informed consent / Invasion and metastasis / Invasiveness / Iron / Lipid peroxidation / Lipids / Male / Matrix Metalloproteinase 2 - metabolism / Matrix Metalloproteinase 9 - metabolism / Medical prognosis / Metabolism / Metastases / Metastasis / Middle Aged / multidisciplinary / N-Cadherin / Neoplasm Invasiveness / Neoplasm Metastasis / Neutropenia / Ovarian cancer / Patients / Peripheral blood / Peripheral blood TfR / Phospholipid Hydroperoxide Glutathione Peroxidase - blood / Proteins / Receptors, Transferrin - blood / Science / Science (multidisciplinary) / Transferrins / Tumors / Urinary Bladder Neoplasms - blood / Urinary Bladder Neoplasms - metabolism / Urinary Bladder Neoplasms - pathology