UroMark-a urinary biomarker assay for the detection of bladder cancer.
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.
UCL Cancer Institute, University College London, London, UK.
Andrew
0000-0001-5282-0498
A
Feber
UCL Cancer Institute, University College London, London, UK.
Pawan
P
Dhami
UCL Cancer Institute, University College London, London, UK.
Liqin
L
Dong
Division of Surgery & Interventional Science, UCL Medical School, University College London, London, UK.
Patricia
P
de Winter
Division of Surgery & Interventional Science, UCL Medical School, University College London, London, UK.
Wei Shen
WS
Tan
Molecular Oncology Unit, CIEMAT (ed70A), Madrid, Spain & Biomedical Research Institute I+12, Universitary Hospistal 12 de Octubre, Av Cordoba s/n. 28041, Madrid, Spain.|Centro de Investigación, Biomédica en Red de Cáncer (CIBER ONC), Madrid, Spain.
Mónica
M
Martínez-Fernández
UCL Cancer Institute, University College London, London, UK.
Dirk S
DS
Paul
Division of Surgery & Interventional Science, UCL Medical School, University College London, London, UK.
Antony
A
Hynes-Allen
UCL Cancer Institute, University College London, London, UK.
Sheida
S
Rezaee
Division of Surgery & Interventional Science, UCL Medical School, University College London, London, UK.|School of Cancer Sciences, University of Birmingham, Birmingham, UK.
Pratik
P
Gurung
Division of Surgery & Interventional Science, UCL Medical School, University College London, London, UK.
Simon
S
Rodney
Division of Surgery & Interventional Science, UCL Medical School, University College London, London, UK.
Ahmed
A
Mehmood
Uro-oncology Section & Biomedical Research Institute I+12, Universitary Hospital 12 de Octubre, Av Córdoba s/n. 28041, Madrid, Spain.|Centro de Investigación, Biomédica en Red de Cáncer (CIBER ONC), Madrid, Spain.
Felipe
F
Villacampa
Uro-oncology Section & Biomedical Research Institute I+12, Universitary Hospital 12 de Octubre, Av Córdoba s/n. 28041, Madrid, Spain.|Centro de Investigación, Biomédica en Red de Cáncer (CIBER ONC), Madrid, Spain.
Federico
F
de la Rosa
Department of Histopathology, University College London Hospital, London, UK.
Charles
C
Jameson
Institute of Applied Health Research, University of Birmingham, Birmingham, UK.
Kar Keung
KK
Cheng
Institute of Applied Health Research, University of Birmingham, Birmingham, UK.|School for Public Health and Primary Care, Maastricht University, Maastricht, Netherlands.
Maurice P
MP
Zeegers
School of Cancer Sciences, University of Birmingham, Birmingham, UK.
Richard T
RT
Bryan
Cancer Research Unit, University of Warwick, Coventry, UK.
Nicholas D
ND
James
Molecular Oncology Unit, CIEMAT (ed70A), Madrid, Spain & Biomedical Research Institute I+12, Universitary Hospistal 12 de Octubre, Av Cordoba s/n. 28041, Madrid, Spain.|Centro de Investigación, Biomédica en Red de Cáncer (CIBER ONC), Madrid, Spain.
Jesus M
JM
Paramio
Department of Histopathology, University College London Hospital, London, UK.
Alex
A
Freeman
UCL Cancer Institute, University College London, London, UK.
Stephan
S
Beck
UCL Cancer Institute, University College London, London, UK.|Division of Surgery & Interventional Science, UCL Medical School, University College London, London, UK.
John D
JD
Kelly
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000652:urine*; D018899:CpG Islands; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000652:urine*; D055088:Early Detection of Cancer; D044127:Epigenesis, Genetic; D005260:Female; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods; D006801:Humans; D008297:Male; D008875:Middle Aged; D017422:Sequence Analysis, DNA / Q000379:methods; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000652:urine*; D055815:Young Adult
D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm
Bladder cancer; Diagnostic; Epigenetics; Next generation sequencing; Urine