Introduction: Prostate cancer (PCa) is common in aging males, diagnosed via the Gleason grading system. The study explores the unexamined prognostic value of cuprotosis, a distinct cell death type, alongside Gleason grades in PCa.

Methods: We explored Cuprotosis-related genes (CRGs) in prostate cancer (PCa), using NMF on TCGA-PRAD data for patient classification and WGCNA to link genes with Gleason scores and prognosis. A risk model was crafted via LASSO Cox regression. STX3 knockdown in PC-3 cells, analyzed for effects on cell behaviors and tumor growth in mice, highlighted its potential therapeutic impact.

Results: We identified five genes crucial for a prognostic risk model, with higher risk scores indicating worse prognosis. Survival analysis and ROC curves confirmed the model's predictive accuracy in TCGA-PRAD and GSE70769 datasets. STX3 was a key adverse prognostic factor, with its knockdown significantly reducing mRNA and protein levels, impairing PC-3 cell functions. In vivo, STX3 knockdown in PC-3 cells led to significantly smaller tumors in nude mice, underscoring its potential therapeutic value.

Conclusion: Our prognostic model, using five genes linked to Gleason scores, effectively predicts prostate cancer outcomes, offering a novel treatment strategy angle.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11291559PMC
http://dx.doi.org/10.1007/s00432-024-05899-9DOI Listing

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