PD46-07 URINARY DNA METHYLATION BIOMARKERS: A NON-INVASIVE METHOD FOR PROSTATE CANCER MONITORING

Abstract

INTRODUCTION AND OBJECTIVES: The majority of men with prostate cancer (PCa) are diagnosed with low-risk disease given effective PSA screening. To avoid over-treatment, men with low-risk PCa are encouraged to be followed on an Active Surveillance (AS) protocol in which repeated blood tests, digital rectal examinations (DRE) and prostate biopsies are utilized to monitor disease progression. Aberrant DNA methylation is a common feature in a variety of tumours. Tumour-specific gene methylation would be an ideal biomarker since only minute amounts of DNA are required which could be extracted from post-DRE urine samples, thus being a much less invasive method for PCa screening as compared to frequent biopsies. Our group previously identified and validated a panel of DNA methylation biomarkers that predicted the presence of high risk disease and/or post treatment biochemical recurrence in radical prostatectomy samples. In the current study, we investigated if this same panel of biomarkers can be detected in post-DRE urine samples of PCa patients participating in an AS program, and whether methylation of these biomarkers could have prognostic value in predicting development of high-risk PCa. METHODS: We collected post DRE urine samples from PCa patients with lowand intermediate-risk PCa patients followed in an AS program. DNA extracted from urine cell pellets was analyzed for selected methylation biomarkers by multiplex MethyLight, a highly sensitive, methylation specific qPCR assay. Patients were stratified using Chi-square analysis by the percent of methylated reference (PMR). Correlative studies were performed on methylation data and clinical variables such as Gleason score and clinical stage. RESULTS: DNA extracted from DRE urine cell pellets of 142 patients was analyzed for the presence of 9 DNA methylation biomarkers. DNA methylation in one or more biomarkers was seen in 73% of patients. Methylation of 3 independent biomarkers was able to distinguish between low(GS6) and intermediate-risk (GS7) PCa (p<0.05). Multigene analysis showed that methylation in a combination of any 3 genes was able to stratify between GS6 and GS7 patients (p<0.05). CONCLUSIONS: We have demonstrated that our panel of DNA methylation biomarkers can be detected in DRE urine samples of PCa patients. These markers have prognostic value in distinguishing low-risk vs intermediate risk PCa. The promising results from this study may help establish a less invasive method for PCa monitoring for patients in AS programs, resulting in better management and treatment for PCa patients.