Oxidative stress-related signature predicts biochemical recurrence and identifies LAMP5 as a candidate prognostic biomarker in prostate cancer

Abstract

Oxidative stress (OS) has been implicated in the malignant progression of prostate cancer (PCa). Biochemical recurrence (BCR) in PCa patients is closely associated with OS. This study aimed to develop a BCR risk predictive model for PCa by screening OS-related biomarkers and preliminarily validating their roles in PCa progression. RNA-seq data from 495 PCa samples and 151 normal prostate tissues were obtained from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases to identify differentially expressed genes (DEGs) between tumor and normal tissues. Single-cell RNA-seq data from the Gene Expression Omnibus (GEO) were analyzed using the R package "Seurat" for cell type identification, and OS response-related genes combined with the "AUCell" package were applied to screen OS-active subgroups and their marker genes. The intersection genes between DEGs and OS-active subgroup markers were used to construct a Biochemical Recurrence Risk Score (BCRRS) model through LASSO regression analysis, which was subsequently validated and evaluated for its predictive value. Random forest analysis and immune checkpoint gene correlation analysis were conducted to identify target genes, followed by in vitro experiments to examine the effects of targeted knockdown on PCa cell proliferation, migration, and invasion. The BCRRS model demonstrated reliable and stable predictive value for BCR in PCa patients, with potential differences in tumor-infiltrating immune cell composition observed between high- and low-risk groups. LAMP5 was identified as a critical predictor of BCR in PCa, and its knockdown markedly decreased the proliferation, migration, and invasion abilities of PC3 and DU145 cells. In conclusion, the BCRRS model constructed based on OS-related biomarkers exhibits robust predictive value, and LAMP5 is a candidate prognostic biomarker whose siRNA-mediated knockdown was associated with reduced proliferation, migration, and invasion in PC3 and DU145 cells.