Multiple omics analyses and experiments validation identify PRDX3 as a biomarker of prognosis and antioncogene in kidney clear cell carcinoma

Peroxiredoxin 3 (PRDX3), a key mitochondrial redox enzyme, has been implicated in malignant tumor initiation and development. However, the its biological function and clinical relevance remain unclear. Here, we performed a systematic pan-cancer analysis of PRDX3 across 33 cancers using The Cancer Genome Atlas database, examining its expression patterns, gene alterations and mutations, methylation, subcellular localization, signaling pathways, tumor microenvironment, immune infiltration, and associations with clinical outcomes. We further validated the biological function role of PRDX3 in kidney clear cell carcinoma (KIRC) through reverse transcription quantitative polymerase chain reaction, Western blotting, Transwell assays, and scratch assays. PRDX3 was differentially expressed in cancers, and its expression appeared to be influenced by copy number variation and methylation status. PRDX3 levels were significantly associated with patient prognosis in multiple tumor types, suggesting context-dependent roles in tumor biology. Functional analyses indicated that PRDX3 may affect tumor progression through programs related to cell-cycle regulation, metabolism, and redox processes. In KIRC models, PRDX3 overexpression suppressed malignant phenotypes and was accompanied by changes in PPAR signaling pathway. Collectively, our results support PRDX3 as potential prognostic biomarker and suggest a tumor-suppressive role in KIRC, although further mechanistic and in vivo validation is warranted.