Single-cell sequencing combined with urinary multi-omics analysis reveals that the non-invasive biomarker PRDX5 regulates bladder cancer progression through ferroptosis signaling.

Abstract

Objective: This study aimed to elucidate the expression profile and biological implications of peroxidase 5 (PRDX5) in bladder cancer (BC), specifically investigating its influence on BC progression through modulation of reactive oxygen species (ROS) levels and activation of ferroptosis pathways.

Methods: We employed urine proteomics data and transcriptomic information from the Cancer Genome Atlas (TCGA) to identify differentially expressed genes in BC tissues, focusing on PRDX5. Using single-cell RNA sequencing (scRNA-seq), we assessed PRDX5 distribution across various cell types in the tumor microenvironment. We conducted in vitro experiments to analyze the impact of PRDX5 on BC cell proliferation, migration, and invasion, while exploring its mechanisms of modulating ROS levels and ferroptosis. In vivo experiments were performed to observe PRDX5's influence on ferroptosis signaling in tissue contexts.

Results: We found significant upregulation of PRDX5 in BC tissues, with scRNA-seq revealing its enrichment in bladder epithelial cells, correlating with disease advancement and established BC markers. In vitro analyses showed that overexpressed PRDX5 enhanced proliferation, migration, and invasion of BC cells, while PRDX5 knockout produced opposing effects. Additionally, PRDX5 modulated ROS levels and impacted ferroptosis pathways. In vivo experiments confirmed that PRDX5 knockout inhibited tumor growth and activated ferroptosis signaling pathways in tissues.

Conclusion: Our study highlights the elevated expression of PRDX5 in BC and its role in promoting tumor progression through regulation of ROS levels and ferroptosis. PRDX5 may serve as a promising target for BC treatment, supporting further exploration of its potential in clinical applications.