Development and validation of a two-gene urine DNA methylation assay for noninvasive prostate cancer detection: a prospective multicenter study.
Summary
A new study developed and validated a non-invasive urine DNA methylation assay for prostate cancer detection, aiming to improve the specificity of PSA screening. This test, based on the methylation of two genes (ADD3 and GSX2), was developed retrospectively in 348 participants and prospectively validated in 200 participants in a multicenter study. It demonstrated robust diagnostic performance with AUCs of 0.86 and 0.91, and specificity above 90%. Integrating this tool could potentially avert approximately 55% of unnecessary biopsies without compromising cancer detection.
Analysis
Clinique : This prospective multicenter validation study (implicitly phase II/III for a diagnostic biomarker) presents a promising predictive biomarker for prostate cancer biopsy decision-making, especially within the PSA gray zone. The two-gene urine test (ADD3_2 and GSX2_2) could significantly reduce (approximately 55%) unnecessary biopsies, thereby improving patient quality of life and reducing healthcare costs. Clinical impact could be observed in the medium term (3-5 years) if larger studies confirm these results, potentially leading to changes in screening guidelines. Biomol : The discovery is based on identifying prostate cancer-specific hypermethylated regions in the ADD3 and GSX2 genes, using an approach combining MeDIP-seq with large-scale public methylome cohorts. The technology used for the final assay is quantitative qPCR, applied to post-prostatic massage urine samples, making it a non-invasive and potentially highly scalable method. The assay demonstrated robust analytical validity with high AUCs (0.86 and 0.91) and >90% specificity, even for clinically significant PCa. The use of urine samples simplifies collection and could facilitate its clinical deployment as a complementary test to PSA.