NADPH Oxidase 4 in Prostate Cancer: Expression and Potential Role in Ferroptosis

Abstract

Prostate cancer (PCa), the most common male malignant tumor worldwide, is associated with high morbidity and mortality, particularly when it progresses to metastatic disease. Ferroptosis, an iron-dependent form of cell death, has been implicated in various cancers. This study investigated the role of NADPH oxidase 4 (NOX4) in PCa and its potential connection to ferroptosis. By analyzing mRNA expression data from TCGA and GEO, NOX4 was found to be significantly upregulated in PCa tissues compared to non-cancerous tissues (SMD = 0.75, 95% CI: 0.41–1.10) and exhibited a moderate diagnostic accuracy (AUC = 0.79, 95% CI: 0.75–0.82). A total of 464 differentially co-expressed genes (DCEGs) were identified, including the hub genes BUB1, CCNB1, and CCNB2. Furthermore, NOX4 expression showed significant correlations with ferroptosisrelated genes such as ALOX15, UBC, FTH1, and SLC2A6. Functional enrichment analyses (GO and KEGG) revealed that NOX4-associated DCEGs were enriched in metabolic pathways, cell cycle regulation, mitotic nuclear division, chromatin binding, and centromeric regions. These results suggest that NOX4 may contribute to ferroptosis regulation in PCa through its involvement in meta-bolic and cell cycle pathways, highlighting its potential as a therapeutic target.