Development and validation of a two-gene urine DNA methylation assay for noninvasive prostate cancer detection: a prospective multicenter study.

Authors

Dingwen Liu, Lian Tang, Wei Xiong, Ran Xu, Qing Zhou, Genming Xu, Zhen Li, Wei Tang, Jinru Feng, Xiaowei Zeng, Jinlei Liu, Chao Li, Lei Chen, Long Wang

Published in

Molecular biomedicine. Volume 7. Issue 1. Aug 07, 2026. Epub Aug 07, 2026.

Abstract

Prostate-specific antigen (PSA) screening lacks specificity, particularly within the 4-10 ng/mL diagnostic gray zone, leading to unnecessary prostate biopsies and overtreatment. Here, we developed and validated a streamlined urine DNA methylation assay for non-invasive prostate cancer (PCa) detection and biopsy decision-making. Tissue-based Methylated DNA Immunoprecipitation Sequencing (MeDIP-seq) was integrated with large-scale public methylome cohorts to identify PCa-specific hypermethylated regions. Candidate markers were further refined by targeted bisulfite sequencing (TBS) and translated into quantitative PCR (qPCR) assays using post-prostatic massage urine samples. In a retrospective development cohort of 348 participants, stepwise marker selection and logistic regression modelling generated a compact two-gene methylation assay comprising ADD3_2 and GSX2_2. The model was then evaluated in an independent prospective multicenter cohort of 200 participants. The assay achieved robust diagnostic performance, with areas under curve (AUC) of 0.86 in the development cohort and 0.91 in the validation cohort, while maintaining specificity above 90%. Performance was preserved in the PSA gray zone and for clinically significant PCa (csPCa). Decision curve analysis (DCA) indicated that integrating this tool could safely avert approximately 55% of unnecessary biopsies without compromising cancer detection. This simple qPCR-based two-gene urine methylation assay provides a scalable, cost-effective and non-invasive complement to PSA-based PCa screening.

PMID:
42566108
Bibliographic data and abstract were imported from PubMed on 07 Aug 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.