PRDM6 promoter methylation as a potential epigenetic biomarker in BRCA-associated ovarian cancer

Background: Ovarian cancer (OC) remains one of the most lethal gynecologic malignancies, primarily due to late-stage diagnosis. Aberrant DNA methylation is critical in tumorigenesis and represents a promising avenue for biomarker development. We hypothesized that PR/SET domain 6 (PRDM6) methylation is associated with breast cancer gene (BRCA) mutation status in OC. Methods: Peripheral blood samples were collected from 387 patients with high-grade serous ovarian cancer, 50 individuals with benign ovarian conditions, and 100 healthy controls. DNA methylation was evaluated using methylation-sensitive restriction enzymes (MSREs) and subsequently analyzed by real-time polymerase chain reaction (PCR). Descriptive statistics were employed to summarize categorical and continuous variables. Associations between PRDM6 methylation and clinical parameters, including BRCA mutation status, cancer antigen 125 (CA-125) levels, and age, were statistically analyzed. Results: PRDM6 methylation was detected in 53.9% of OC patients, 60.0% of individuals with benign ovarian disease, and 37.0% of healthy controls. The methylation frequency in OC patients was significantly higher than in healthy controls (p = 0.005). PRDM6 promoter methylation was detected in 64.8% of BRCA-mutated OC patients compared to 50.3% of BRCA negative patients, indicating a significant association between BRCA mutation status and PRDM6 methylation (p = 0.016). No significant associations were found between PRDM6 methylation and age, menopausal status, or CA-125 levels. Conclusions: PRDM6 methylation may serve as a non-invasive biomarker for early detection in high risk populations, particularly in BRCA mutation carriers.