CRMP4 CpG Hypermethylation Predicts Upgrading to Gleason Score ≥ 8 in Prostate Cancer

Area of Science:

• Urology
• Oncology
• Molecular Diagnostics

Background:

• Prostate cancer (PCa) risk stratification is crucial for treatment.
• Low-risk PCa patients may experience postoperative Gleason Score (GS) upgrades.
• Accurate prediction of GS upgrade is essential to avoid overtreatment or undertreatment.

Purpose of the Study:

• To determine the predictive value of CRMP4 promoter methylation in core needle biopsies.
• To assess if CRMP4 methylation can predict Gleason Score (GS) upgrade to ≥8 post-radical prostatectomy (RP).
• To identify a threshold for CRMP4 methylation indicating increased risk.

Main Methods:

• Retrospective analysis of 631 low-risk PCa patients undergoing RP.
• Detection of CRMP4 promoter methylation in core needle biopsy specimens.
• Logistic regression and ROC curve analysis to identify predictive factors and cut-off values.

Main Results:

• CRMP4 promoter methylation, prostate volume, and number of positive cores predicted GS upgrade (P<0.001).
• A CRMP4 methylation rate >18.00% was associated with a higher likelihood of upgrade.
• High predictive rates (positive 85.2%, negative 99.3%, overall 97.9%) and AUC of 0.929 were achieved.
• CRMP4 methylation >18.0% correlated with worse biochemical recurrence-free, progression-free, and cancer-specific survival.

Conclusions:

• CRMP4 promoter methylation is a significant predictor of Gleason Score upgrade in low-risk PCa.
• A CRMP4 methylation rate exceeding 18.00% suggests a transition to high-risk disease.
• Pre-operative CRMP4 methylation assessment is recommended for low-risk PCa patients before RP.