Comparison and combination of mutation and methylation-based urine tests for bladder cancer detection.

Autor: Gordon NS; The Bladder Cancer Research Centre, Department of Cancer and Genomic Sciences, College of Medicine and Health, University of Birmingham, Birmingham, B15 2TT, UK., McGuigan EK; The Bladder Cancer Research Centre, Department of Cancer and Genomic Sciences, College of Medicine and Health, University of Birmingham, Birmingham, B15 2TT, UK., Ondasova M; The Bladder Cancer Research Centre, Department of Cancer and Genomic Sciences, College of Medicine and Health, University of Birmingham, Birmingham, B15 2TT, UK., Knight J; The Bladder Cancer Research Centre, Department of Cancer and Genomic Sciences, College of Medicine and Health, University of Birmingham, Birmingham, B15 2TT, UK., Baxter LA; Bioinformatics & Digital Health Services, Research Technology Platforms, University of Warwick, Coventry, CV4 7AL, UK., Ott S; Bioinformatics & Digital Health Services, Research Technology Platforms, University of Warwick, Coventry, CV4 7AL, UK., Hastings RK; Nonacus Ltd, Unit 5, Quinton Business Park, Birmingham, B32 1AF, UK., Zeegers MP; Department of Epidemiology, School of Nutrition and Translational Research in Metabolism, University of Maastricht, Maastricht, The Netherlands., James ND; The Institute of Cancer Research, London, SM2 5NG, UK., Cheng KK; Department of Applied health Sciences, College of Medicine and Health, University of Birmingham, Birmingham, B15 2TT, UK., Goel A; The Bladder Cancer Research Centre, Department of Cancer and Genomic Sciences, College of Medicine and Health, University of Birmingham, Birmingham, B15 2TT, UK., Yu M; The Bladder Cancer Research Centre, Department of Cancer and Genomic Sciences, College of Medicine and Health, University of Birmingham, Birmingham, B15 2TT, UK., Arnold R; The Bladder Cancer Research Centre, Department of Cancer and Genomic Sciences, College of Medicine and Health, University of Birmingham, Birmingham, B15 2TT, UK., Bryan RT; The Bladder Cancer Research Centre, Department of Cancer and Genomic Sciences, College of Medicine and Health, University of Birmingham, Birmingham, B15 2TT, UK., Ward DG; The Bladder Cancer Research Centre, Department of Cancer and Genomic Sciences, College of Medicine and Health, University of Birmingham, Birmingham, B15 2TT, UK. d.g.ward@bham.ac.uk.
Jazyk: angličtina
Zdroj: Biomarker research [Biomark Res] 2024 Nov 07; Vol. 12 (1), pp. 133. Date of Electronic Publication: 2024 Nov 07.
DOI: 10.1186/s40364-024-00682-x
Abstrakt: Background and Aims: Several non-invasive tests for detecting bladder cancer (BC) are commercially available and are based on detecting small panels of BC-associated mutations and/or methylation changes in urine DNA. However, it is not clear which type of biomarker is best, or if a combination of the two is needed. In this study we address this question by taking a 23-gene mutation panel (GALEAS™ Bladder, GB) and testing if adding a panel of methylation markers improves the sensitivity of BC detection.
Methods: Twenty-three methylation markers were assessed in urine DNA by bisulphite conversion, multiplex PCR, and next generation sequencing in 118 randomly selected haematuria patients with pre-existing GB data (56 BCs and 62 non-BCs), split into training and test sets. We also analysed an additional 16 GB false-negative urine DNAs.
Results: The methylation panel detected bladder cancer in haematuria patients with 69% sensitivity at 96% specificity (test set results, 95% CIs 52-87% and 80-99%, respectively). Corresponding sensitivity and specificity for GB were 92% and 89%. Methylation and mutation markers were highly concordant in urine, with all GB false-negative samples also negative for methylation markers.
Conclusions and Limitations: Our data show that, with a comprehensive mutation panel, any gains from adding methylation markers are, at best, marginal. It is likely that low tumour content is the commonest cause of false-negative urine test results. Our study does have a limited sample size and other methylation markers might behave differently to the those studied here.
(© 2024. The Author(s).)
Databáze: MEDLINE
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