Nrf2 Gene and Keap1 Enzyme Levels in Bladder Cancer

Year 2026, Volume: 7 Issue: 1, 11 - 16, 04.01.2026

Mehmet Aydın Dağdeviren , Ömer Eronat , Mehmet Özaslan

https://doi.org/10.55549/zbs.1792568

Abstract

Bladder cancer is a prevalent urological malignancy, particularly in developed countries, and occurs more frequently in men. Tumor initiation and progression involve multiple molecular pathways, including the Nuclear factor erythroid 2–related factor 2 (NRF2) pathway, which regulates cellular antioxidant and detoxification responses. NRF2 activity is negatively controlled by Kelch-like ECH-associated protein 1 (KEAP1), which retains NRF2 in the cytoplasm and targets it for proteasomal degradation under physiological conditions. In response to oxidative stress, NRF2 dissociates from KEAP1, translocates to the nucleus, and activates transcription of protective genes. Dysregulation of this pathway has been implicated in various cancers, including bladder cancer, contributing to increased proliferation, chemotherapy resistance, and apoptosis evasion. Consequently, the NRF2–KEAP1 axis represents a key target for understanding tumor biology and developing novel therapeutic strategies. In this study, the role of NRF2 and KEAP1 proteins in bladder cancer pathogenesis was investigated. Tissue samples from 45 low-grade and 45 high-grade bladder tumors were analyzed, and protein levels were quantitatively measured using ELISA. High-grade tumors exhibited significantly elevated KEAP1 and NRF2 levels compared to low-grade tumors (p < 0.001 and p < 0.05, respectively). Moreover, a statistically significant positive correlation was observed between KEAP1 and NRF2 levels (p < 0.05). These results suggest that the KEAP1–NRF2 signaling pathway is closely associated with tumor grade and may serve as a potential biomarker and therapeutic target in bladder cancer progression.

Keywords

Bladder cancer , KEAP1 , NRF2 , Oxidative stress , Signaling pathway , ELISA

Ethical Statement

Ethical approval for this study was obtained from the Ethics Committee of Gaziantep University

Supporting Institution

Gaziantep University Scientific Research Unit (BAP)

Project Number

Approval No: 2024/51

Thanks

This study was supported by the Scientific Research Projects Coordination Unit of Gaziantep University (Project Code: FEF.HZP.24.06). We would like to thank all researchers who contributed to the study and the Gaziantep University Application and Research Center for their support.

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