Bladder cancer detection in urine using DNA methylation markers: a technical and prospective preclinical validation

• Published in: Clinical epigenetics 2022-02, Vol.14 (1), p.19-19, Article 19
• Main Authors: Hentschel, Anouk E, Beijert, Irene J, Bosschieter, Judith, Kauer, Paul C, Vis, André N, Lissenberg-Witte, Birgit I, van Moorselaar, R Jeroen A, Steenbergen, Renske D M, Nieuwenhuijzen, Jakko A
• Format: Article
• Language: English
• Subjects: Aged; Area Under Curve; Biomarkers; Biomarkers - analysis; Biomarkers - urine; Bladder cancer; Cancer; Cellular biology; Comparative analysis; Deoxyribonucleic acid; Diagnosis; DNA; DNA methylation; DNA Methylation - genetics; Early Detection of Cancer - methods; Early Detection of Cancer - statistics & numerical data; Female; Gender; Genetic aspects; Genetic research; Hematuria; Humans; Male; Methylation; Middle Aged; Netherlands - epidemiology; Oncology, Experimental; Patients; Population studies; Prospective Studies; ROC Curve; Sample size; Sensitivity and Specificity; Software; Tumors; Urinary Bladder Neoplasms - diagnosis; Urinary Bladder Neoplasms - epidemiology; Urinary Bladder Neoplasms - urine; Urine
• ISSN: 1868-7075; 1868-7083; 1868-7083; 1868-7075
• DOI: 10.1186/s13148-022-01240-8

The development of accurate urinary biomarkers for non-invasive and cost-effective detection of primary and recurrent bladder tumours is recognized as one of the major clinical needs in bladder cancer diagnostics. The purposes of this study were (1) to validate the results of a previous technical comparison by determining the diagnostic performance of nine methylation markers in urine pellet compared to full void urine, and (2) to validate the diagnostic performance of the optimal marker panel GHSR/MAL from a previous exploratory study in a preclinical setting. Urine samples of 108 patients with bladder cancer and 100 age- and gender-matched controls were prospectively collected for methylation analysis. Urinary methylation levels of the markers FAM19A4, GHSR, MAL, miR-129, miR-935, PHACTR3, PRDM14, SST and ZIC1 were determined with quantitative methylation-specific PCR in urine pellet. Area under the curves (AUCs) were determined for individual markers and the marker panel GHSR/MAL. The diagnostic performance of the marker panel GHSR/MAL was evaluated in the total study population and in different subgroups of patients with bladder cancer using the Chi-square test. The diagnostic accuracy was assessed by leave-one-out cross-validation. All nine urinary methylation markers (FAM19A4, GHSR, MAL, miR-129, miR-935, PHACTR3, PRDM14, SST and ZIC1) showed significantly higher methylation levels in bladder cancer patients than in controls (p