Dysregulated Peroxiredoxins in Bladder Cancer Are Associated With an Altered Tumour Immune Microenvironment

Abstract

Peroxiredoxins (PRDXs) are antioxidant enzymes that scavenge hydrogen peroxide and protect cells from reactive oxygen species (ROS). There are six genes encode different types of PRDXs (PRDX1-PRDX6) in humans and most of them are overexpressed in tumours; however, their expression patterns and prognostic value in bladder cancer (BLCA) remain unclear. In this study, we examined the aberrant expression of all six types of PRDX genes in BLCA and identified distinct clinical and immune associations. High expression of PRDX1 and PRDX6 was correlated with poor overall survival (OS), increased mutational burden and chromosomal instability. Overexpression of PRDX4 and PRDX6 was associated with advanced tumour stage, larger tumour size, higher immune scores, and increased immune cell infiltration. By contrast, PRDX2 overexpression showed only modest effects on OS and was associated with reduced immune signalling and diminished infiltration of anti-tumor immune cells. These findings highlight the differential roles of PRDX family members in shaping BLCA tumour immune microenvironment. PRDXs may serve as prognostic biomarkers for patients tratification and represent potential therapeutic targets to enhance immunotherapy response. Further in vitro and in vivo studies are required to confirm our in silico data and define their clinical relevance for BLCA prognosis.