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.
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.
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.
Clinical epigenetics. 2017 Jan 31*** epublish ***
Andrew Feber, Pawan Dhami, Liqin Dong, Patricia de Winter, Wei Shen Tan, Mónica Martínez-Fernández, Dirk S Paul, Antony Hynes-Allen, Sheida Rezaee, Pratik Gurung, Simon Rodney, Ahmed Mehmood, Felipe Villacampa, Federico de la Rosa, Charles Jameson, Kar Keung Cheng, Maurice P Zeegers, Richard T Bryan, Nicholas D James, Jesus M Paramio, Alex Freeman, Stephan Beck, John D Kelly
UCL Cancer Institute, University College London, London, UK., Division of Surgery & Interventional Science, UCL Medical School, University College London, London, UK., Molecular Oncology Unit, CIEMAT (ed70A), Madrid, Spain & Biomedical Research Institute I+12, Universitary Hospistal 12 de Octubre, Av Cordoba s/n. 28041, Madrid, Spain., Uro-oncology Section & Biomedical Research Institute I+12, Universitary Hospital 12 de Octubre, Av Córdoba s/n. 28041, Madrid, Spain., Department of Histopathology, University College London Hospital, London, UK., Institute of Applied Health Research, University of Birmingham, Birmingham, UK., School of Cancer Sciences, University of Birmingham, Birmingham, UK., Cancer Research Unit, University of Warwick, Coventry, UK.