Biomarker Research (Nov 2024)

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

  • 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

DOI
https://doi.org/10.1186/s40364-024-00682-x
Journal volume & issue
Vol. 12, no. 1
pp. 1 – 4

Abstract

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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.

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