UroMark - A urinary biomarker assay for the detection of bladder cancer

Research output: Contribution to journalArticle

Authors

  • Andrew Feber
  • Pawan Dhami
  • Liqin Dong
  • Patricia de Winter
  • Wei Shen Tan
  • Monica Martínez-Fernández
  • Dirk Paul
  • Antony Hynes-Allen
  • Sheida Rezaee
  • Pratik Gurung
  • Simon Rodney
  • Ahmed Mehmood
  • Felipe Villacampa
  • Federico de la Rosa
  • Charles Jameson
  • Jesus Paramio
  • Alex Freeman
  • Stephan Beck
  • John Kelly

Abstract

Background
Bladder cancer (BC) is one of the most common cancers in the western world and ranks as the most expensive to manage, due to the need for cystoscopic examination. BC shows frequent changes in DNA methylation, and several studies have shown the potential utility of urinary biomarkers by detecting epigenetic alterations in voided urine. The aim of this study is to develop a targeted bisulfite next-generation sequencing assay to diagnose BC from urine with high sensitivity and specificity.

Results
We defined a 150 CpG loci biomarker panel from a cohort of 86 muscle-invasive bladder cancers and 30 normal urothelium. Based on this panel, we developed the UroMark assay, a next-generation bisulphite sequencing assay and analysis pipeline for the detection of bladder cancer from urinary sediment DNA. The 150 loci UroMark assay was validated in an independent cohort (n = 274, non-cancer (n = 167) and bladder cancer (n = 107)) voided urine samples with an AUC of 97%. The UroMark classifier sensitivity of 98%, specificity of 97% and NPV of 97% for the detection of primary BC was compared to non-BC urine.

Conclusions
Epigenetic urinary biomarkers for detection of BC have the potential to revolutionise the management of this disease. In this proof of concept study, we show the development and utility of a novel high-throughput, next-generation sequencing-based biomarker for the detection of BC-specific epigenetic alterations in urine.

Details

Original languageEnglish
Article number8
JournalClinical epigenetics
Volume9
Early online date31 Jan 2017
Publication statusE-pub ahead of print - 31 Jan 2017

Keywords

  • Bladder cancer, Epigenetics, Urine, Next generation sequencing, Diagnostic