Identification of a Cuproptosis-Related Molecular Signature for Predicting Biochemical Recurrence in Prostate Cancer

Area of Science:

• Oncology
• Genomics
• Immunology

Background:

• Prostate cancer (PCa) prognosis and tumor immune microenvironment (TIME) characterization are critical for effective management.
• Cuproptosis-related genes (CRGs) are increasingly recognized for their role in cancer progression and immune response.

Purpose of the Study:

• To develop and validate a CRG-based signature for predicting biochemical recurrence-free survival (BCRFS) in PCa.
• To characterize the TIME in PCa using CRGs and assess the signature's correlation with immune features.

Main Methods:

• Transcriptomic data from TCGA (n=405) and GEO (n=203) cohorts were analyzed.
• Consensus clustering identified molecular subtypes based on 10 CRGs.
• LASSO Cox regression constructed a six-gene prognostic signature (CALML5, MMP11, UBE2C, ANPEP, TMEM59L, COMP).
• Quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC) were used for experimental validation.

Main Results:

• Two CRG-based molecular subtypes with distinct clinicopathological features and BCRFS were identified.
• The six-gene signature stratified PCa patients into high- and low-risk groups with significantly different BCRFS (P<0.001).
• The signature demonstrated good predictive accuracy (AUCs up to 0.837) and was independent of clinicopathological factors.
• High-risk patients showed elevated immune/stromal scores, altered immune infiltration, and higher immune checkpoint expression.
• Experimental validation confirmed differential expression of the six genes in PCa tissues and cell lines.

Conclusions:

• A novel six-gene CRG signature effectively predicts BCRFS and reflects immune heterogeneity in PCa.
• This signature can potentially guide personalized treatment strategies and immunotherapy in PCa.
• Further validation in prospective clinical studies is warranted.