Comparison and combination of mutation and methylation-based urine tests for bladder cancer detection
Abstract 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 combinati...
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BMC
2024-11-01
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| Series: | Biomarker Research |
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| Online Access: | https://doi.org/10.1186/s40364-024-00682-x |
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| author | Naheema S. Gordon Elspeth K. McGuigan Michaela Ondasova Jennifer Knight Laura A. Baxter Sascha Ott Robert K. Hastings Maurice P. Zeegers Nicholas D. James K. K. Cheng Anshita Goel Minghao Yu Roland Arnold Richard T. Bryan Douglas G. Ward |
| author_facet | Naheema S. Gordon Elspeth K. McGuigan Michaela Ondasova Jennifer Knight Laura A. Baxter Sascha Ott Robert K. Hastings Maurice P. Zeegers Nicholas D. James K. K. Cheng Anshita Goel Minghao Yu Roland Arnold Richard T. Bryan Douglas G. Ward |
| author_sort | Naheema S. Gordon |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
| id | doaj-art-948476a9f2e2449e9f9c0f8d0705374d |
| institution | OA Journals |
| issn | 2050-7771 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Biomarker Research |
| spelling | doaj-art-948476a9f2e2449e9f9c0f8d0705374d2025-08-20T02:13:26ZengBMCBiomarker Research2050-77712024-11-011211410.1186/s40364-024-00682-xComparison and combination of mutation and methylation-based urine tests for bladder cancer detectionNaheema S. Gordon0Elspeth K. McGuigan1Michaela Ondasova2Jennifer Knight3Laura A. Baxter4Sascha Ott5Robert K. Hastings6Maurice P. Zeegers7Nicholas D. James8K. K. Cheng9Anshita Goel10Minghao Yu11Roland Arnold12Richard T. Bryan13Douglas G. Ward14The Bladder Cancer Research Centre, Department of Cancer and Genomic Sciences, College of Medicine and Health, University of BirminghamThe Bladder Cancer Research Centre, Department of Cancer and Genomic Sciences, College of Medicine and Health, University of BirminghamThe Bladder Cancer Research Centre, Department of Cancer and Genomic Sciences, College of Medicine and Health, University of BirminghamThe Bladder Cancer Research Centre, Department of Cancer and Genomic Sciences, College of Medicine and Health, University of BirminghamBioinformatics & Digital Health Services, Research Technology Platforms, University of WarwickBioinformatics & Digital Health Services, Research Technology Platforms, University of WarwickNonacus Ltd, Unit 5, Quinton Business ParkDepartment of Epidemiology, School of Nutrition and Translational Research in Metabolism, University of MaastrichtThe Institute of Cancer ResearchDepartment of Applied health Sciences, College of Medicine and Health, University of BirminghamThe Bladder Cancer Research Centre, Department of Cancer and Genomic Sciences, College of Medicine and Health, University of BirminghamThe Bladder Cancer Research Centre, Department of Cancer and Genomic Sciences, College of Medicine and Health, University of BirminghamThe Bladder Cancer Research Centre, Department of Cancer and Genomic Sciences, College of Medicine and Health, University of BirminghamThe Bladder Cancer Research Centre, Department of Cancer and Genomic Sciences, College of Medicine and Health, University of BirminghamThe Bladder Cancer Research Centre, Department of Cancer and Genomic Sciences, College of Medicine and Health, University of BirminghamAbstract 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.https://doi.org/10.1186/s40364-024-00682-xBladder cancerUrine testBiomarkerMutationMethylation |
| spellingShingle | Naheema S. Gordon Elspeth K. McGuigan Michaela Ondasova Jennifer Knight Laura A. Baxter Sascha Ott Robert K. Hastings Maurice P. Zeegers Nicholas D. James K. K. Cheng Anshita Goel Minghao Yu Roland Arnold Richard T. Bryan Douglas G. Ward Comparison and combination of mutation and methylation-based urine tests for bladder cancer detection Biomarker Research Bladder cancer Urine test Biomarker Mutation Methylation |
| title | Comparison and combination of mutation and methylation-based urine tests for bladder cancer detection |
| title_full | Comparison and combination of mutation and methylation-based urine tests for bladder cancer detection |
| title_fullStr | Comparison and combination of mutation and methylation-based urine tests for bladder cancer detection |
| title_full_unstemmed | Comparison and combination of mutation and methylation-based urine tests for bladder cancer detection |
| title_short | Comparison and combination of mutation and methylation-based urine tests for bladder cancer detection |
| title_sort | comparison and combination of mutation and methylation based urine tests for bladder cancer detection |
| topic | Bladder cancer Urine test Biomarker Mutation Methylation |
| url | https://doi.org/10.1186/s40364-024-00682-x |
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