NOX4 suppresses malignant progression in prostate adenocarcinoma and functions as a potential diagnostic biomarker.

Background: Prostate adenocarcinoma (PRAD) is a highly prevalent malignant tumor in males and exhibits substantial heterogeneity. Identifying key associated genes is therefore critical for improving disease diagnosis and therapeutic strategies. Methods: In this study, we first analyzed gene expression profiles to identify differentially expressed genes (DEGs) between PRAD and normal tissues. Subsequently, a weighted gene co-expression network analysis (WGCNA) was performed to elucidate the functional roles and signaling pathways of key genes, supported by Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis (GSEA) enrichment analyses. To prioritize robust diagnostic markers, three machine learning algorithms, least absolute shrinkage and selection operator (LASSO) regression, support vector machine with recursive feature elimination (SVM-RFE), and random forest, were integrated, and their intersection yielded six core genes: Results: Results from the DCFH-DA fluorescence assay showed that NOX4 overexpression significantly elevated intracellular reactive oxygen species (ROS) levels and activated the PI3K/AKT/ERK signaling pathway in PRAD cells. Conclusions: These findings suggest that NOX4 may regulate the redox balance of PRAD cells while activating the PI3K/AKT signaling pathway.