Development, Validation, and Clinical Utility of a Six-gene Signature to Predict Aggressive Prostate Cancer

Area of Science:

• Oncology
• Genomics
• Molecular Diagnostics

Background:

• Prostate cancer (PCa) molecular signatures in tissue offer prognostic insights into aggressive disease risk.
• Accurate risk stratification is crucial for optimizing treatment decisions and patient management in PCa.

Purpose of the Study:

• To develop and validate a novel gene signature for independent prognostic information in PCa.
• To enhance treatment decisions and patient management by integrating molecular data with clinical parameters.

Main Methods:

• Expression analysis of 14 genes in radical prostatectomy (RP) tissue from 426 Irish PCa patients.
• Identification of a six-gene molecular risk score (MRS) and its combination with the CAPRA score to form the MCRS.
• Validation of the MCRS in an independent Swedish cohort of 203 PCa patients.

Main Results:

• The six-gene signature demonstrated significant prognostic performance for adverse pathology (AP) and biochemical recurrence (BCR) (p < 0.0001).
• Both MRS and MCRS significantly improved prognostic accuracy (AUC/C-index) when added to existing scores (EAU, CAPRA).
• The study identified a retrospective design as a limitation.

Conclusions:

• The validated six-gene signature exhibits strong predictive performance for AP and BCR post-RP.
• The MCRS enhances prognostic evaluation, offering potential to optimize patient management strategies.
• This molecular signature provides valuable prognostic information beyond traditional clinical parameters.