Ultra-sensitive urine DNA methylation test enables early and accurate detection of bladder cancer

Résumé fourni par la source

Early and accurate detection of bladder cancer (BCa), particularly low-grade and early-stage disease, remains challenging because current diagnostic methods are either invasive or insufficiently sensitive. We aimed to develop a noninvasive urine DNA methylation assay for BCa detection and postoperative monitoring. Integrative methylation profiling across institutional and public cohorts identified PENK and NKPD1 as urothelial carcinoma-associated hypermethylation markers. A bisulfite-free methylation-sensitive restriction enzyme quantitative polymerase chain reaction (MSRE-qPCR) assay was developed using urine sediment DNA. Diagnostic performance was evaluated in a case-control cohort of 606 urine samples, including 340 pathologically confirmed BCa cases. The dual-marker assay achieved areas under the curve (AUCs) of 92.52% and 93.00% in the training and validation cohorts, respectively. Sensitivity reached 87.74%, with specificity of 92.31% against benign urological diseases and 83.05% against non-urothelial malignancies. The assay outperformed urine cytology in low-grade tumors and provided complementary diagnostic value when combined with cytology. Postoperative methylation signals significantly decreased after tumor resection (p < 0.001). This bisulfite-free urine MSRE-qPCR assay provides a simple and scalable approach for noninvasive BCa detection and surveillance, with strong performance in early-stage and low-grade disease. Further prospective multicenter validation is warranted. Bladder cancer is a common urinary system cancer that often requires repeated examinations and long-term follow-up. Current diagnostic methods, such as cystoscopy, are invasive and uncomfortable for patients, while urine cytology may miss early-stage or low-grade tumors. Therefore, there is a need for simple and reliable noninvasive tests for bladder cancer detection and monitoring. In this study, we developed a urine-based DNA test that detects abnormal DNA changes associated with bladder cancer. The test uses two DNA markers, called PENK and NKPD1, and does not require harsh chemical treatment during the testing process, making the workflow simpler and potentially more stable for clinical use. We evaluated this method using urine samples collected from 606 participants, including patients with bladder cancer, benign urinary diseases, and other urinary system cancers. The test showed high accuracy in distinguishing bladder cancer from noncancer controls. Importantly, it also performed well in early-stage and low-grade tumors, which are often difficult to detect using conventional urine tests. In addition, DNA signal levels decreased after tumor removal surgery, suggesting potential value for postoperative monitoring. Overall, our findings suggest that this urine DNA test may provide a practical and noninvasive approach for bladder cancer detection and follow-up. However, larger prospective multicenter studies are still needed before routine clinical application.

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