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

**Authors:** Jarett Wallerson, Sara Rostampour, Shaolei Teng, Dawit Kidane

PMC · DOI: 10.1111/jcmm.71064 · Journal of Cellular and Molecular Medicine · 2026-02-27

## TL;DR

This study explores how peroxiredoxins (PRDXs) affect bladder cancer survival and immune response, revealing their potential as biomarkers and therapeutic targets.

## Contribution

The study identifies distinct clinical and immune associations of PRDX family members in bladder cancer for the first time.

## Key findings

- High PRDX1 and PRDX6 expression correlates with poor survival and increased mutational burden in bladder cancer.
- PRDX4 and PRDX6 overexpression is linked to advanced tumor stage and increased immune cell infiltration.
- PRDX2 overexpression is associated with reduced immune signaling and fewer anti-tumor immune cells.

## 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.

## Linked entities

- **Genes:** PRDX1 (peroxiredoxin 1) [NCBI Gene 5052], PRDX2 (peroxiredoxin 2) [NCBI Gene 7001], PRDX4 (peroxiredoxin 4) [NCBI Gene 10549], PRDX6 (peroxiredoxin 6) [NCBI Gene 9588]
- **Diseases:** bladder cancer (MONDO:0004986), BLCA (MONDO:0005611)

## Full-text entities

- **Genes:** CD274 (CD274 molecule) [NCBI Gene 29126] {aka ADMIO5, B7-H, B7H1, PD-L1, PDCD1L1, PDCD1LG1}, PRDX1 (peroxiredoxin 1) [NCBI Gene 5052] {aka MSP23, NKEF-A, NKEFA, PAG, PAGA, PAGB}, CD4 (CD4 molecule) [NCBI Gene 920] {aka CD4mut, IMD79, Leu-3, OKT4D, T4}, PRDX5 (peroxiredoxin 5) [NCBI Gene 25824] {aka ACR1, AOEB166, B166, HEL-S-55, PLP, PMP20}, CCL5 (C-C motif chemokine ligand 5) [NCBI Gene 6352] {aka D17S136E, RANTES, SCYA5, SIS-delta, SISd, TCP228}, ARID1A (AT-rich interaction domain 1A) [NCBI Gene 8289] {aka B120, BAF250, BAF250a, BM029, C1orf4, CSS2}, TP53 (tumor protein p53) [NCBI Gene 7157] {aka BCC7, BMFS5, LFS1, P53, TRP53}, CDKN2A (cyclin dependent kinase inhibitor 2A) [NCBI Gene 1029] {aka ARF, CAI2, CDK4I, CDKN2, CMM2, INK4}, PRDX2 (peroxiredoxin 2) [NCBI Gene 7001] {aka HEL-S-2a, NKEF-B, NKEFB, PRP, PRX2, PRXII}, CTLA4 (cytotoxic T-lymphocyte associated protein 4) [NCBI Gene 1493] {aka ALPS5, CD, CD152, CELIAC3, CTLA-4, GRD4}, PRDX3 (peroxiredoxin 3) [NCBI Gene 10935] {aka AOP-1, AOP1, HBC189, MER5, PPPCD, PRO1748}, CXCL10 (C-X-C motif chemokine ligand 10) [NCBI Gene 3627] {aka C7, IFI10, INP10, IP-10, SCYB10, crg-2}, PRDX6 (peroxiredoxin 6) [NCBI Gene 9588] {aka 1-Cys, AOP2, HEL-S-128m, LPCAT-5, NSGPx, PRX}, PDCD1LG2 (programmed cell death 1 ligand 2) [NCBI Gene 80380] {aka B7DC, Btdc, CD273, PD-L2, PDCD1L2, PDL2}, PRDX4 (peroxiredoxin 4) [NCBI Gene 10549] {aka AOE37-2, AOE372, HEL-S-97n, PRX-4}, ISG15 (ISG15 ubiquitin like modifier) [NCBI Gene 9636] {aka G1P2, IFI15, IMD38, IP17, UCRP, hUCRP}, CD8A (CD8 subunit alpha) [NCBI Gene 925] {aka CD8, CD8alpha, IMD116, Leu2, p32}, PDCD1 (programmed cell death 1) [NCBI Gene 5133] {aka ADMIO4, AIMTBS, CD279, PD-1, PD1, SLEB2}
- **Diseases:** carcinogenesis (MESH:D063646), tumour stage III and IV, lymph node and metastasis (MESH:D008207), T3- (MESH:C537047), Allergy and Infectious Diseases (MESH:D003141), non (MESH:C580335), Aneuploidy (MESH:D000782), BLCA metastasis (MESH:D001749), stage III (MESH:D062706), Urothelial carcinoma (MESH:D014523), toxicity (MESH:D064420), NMIBC (MESH:D000093284), Cancer (MESH:D009369)
- **Chemicals:** peroxynitrite (MESH:D030421), GSH (MESH:D005978), ROS (MESH:D017382), acid (MESH:D000143), superoxide (MESH:D013481), hydrogen peroxide (MESH:D006861), CoQ10 (MESH:C024989), peroxide (MESH:D010545)
- **Species:** Homo sapiens (human, species) [taxon 9606]
- **Cell lines:** BLCA — Mus musculus (Mouse), Spontaneously immortalized cell line (CVCL_S780)

## Full text

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## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12948642/full.md

## References

38 references — full list in the complete paper: https://tomesphere.com/paper/PMC12948642/full.md

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Source: https://tomesphere.com/paper/PMC12948642