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

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; Kar Cheng; Maurice Zeegers; Richard Bryan; Nicholas James; Jesus Paramio; Alex Freeman; Stephan Beck; John Kelly

doi:10.1186/s13148-016-0303-5

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

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, Kar Cheng, Maurice Zeegers, Richard Bryan, Nicholas James, Jesus ParamioAlex Freeman, Stephan Beck, John Kelly

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42 Citations (Scopus)

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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.

Original language	English
Article number	8
Number of pages	10
Journal	Clinical epigenetics
Volume	9
DOIs	https://doi.org/10.1186/s13148-016-0303-5
Publication status	Published - 31 Jan 2017

Keywords

Bladder cancer
Epigenetics
Urine
Next generation sequencing
Diagnostic

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Feber_et_al_UroMark_Clinical_Epigenetics_2017Final published version, 3.09 MBLicence: Creative Commons: Attribution (CC BY)

42 Citations
1 Editorial

Liquid biopsies for bladder cancer
Ward, D. & Bryan, R., 30 Apr 2017, In: Translational Andrology and Urology. 6, 2, p. 331-335 5 p.
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Feber, A., Dhami, P., Dong, L., de Winter, P., Tan, W. S., Martínez-Fernández, M., Paul, D., Hynes-Allen, A., Rezaee, S., Gurung, P., Rodney, S., Mehmood, A., Villacampa, F., de la Rosa, F., Jameson, C., Cheng, K., Zeegers, M., Bryan, R., James, N., ... Kelly, J. (2017). UroMark - A urinary biomarker assay for the detection of bladder cancer. Clinical epigenetics, 9, Article 8. https://doi.org/10.1186/s13148-016-0303-5

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title = "UroMark - A urinary biomarker assay for the detection of bladder cancer",

abstract = "BackgroundBladder 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.ResultsWe 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.ConclusionsEpigenetic 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.",

keywords = "Bladder cancer, Epigenetics, Urine, Next generation sequencing, Diagnostic",

author = "Andrew Feber and Pawan Dhami and Liqin Dong and {de Winter}, Patricia and Tan, {Wei Shen} and Monica Mart{\'i}nez-Fern{\'a}ndez and Dirk Paul and Antony Hynes-Allen and Sheida Rezaee and Pratik Gurung and Simon Rodney and Ahmed Mehmood and Felipe Villacampa and {de la Rosa}, Federico and Charles Jameson and Kar Cheng and Maurice Zeegers and Richard Bryan and Nicholas James and Jesus Paramio and Alex Freeman and Stephan Beck and John Kelly",

year = "2017",

month = jan,

day = "31",

doi = "10.1186/s13148-016-0303-5",

language = "English",

volume = "9",

journal = "Clinical epigenetics",

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Feber, A, Dhami, P, Dong, L, de Winter, P, Tan, WS, Martínez-Fernández, M, Paul, D, Hynes-Allen, A, Rezaee, S, Gurung, P, Rodney, S, Mehmood, A, Villacampa, F, de la Rosa, F, Jameson, C, Cheng, K, Zeegers, M, Bryan, R , James, N, Paramio, J, Freeman, A, Beck, S & Kelly, J 2017, 'UroMark - A urinary biomarker assay for the detection of bladder cancer', Clinical epigenetics, vol. 9, 8. https://doi.org/10.1186/s13148-016-0303-5

TY - JOUR

T1 - UroMark - A urinary biomarker assay for the detection of bladder cancer

AU - Feber, Andrew

AU - Dhami, Pawan

AU - Dong, Liqin

AU - de Winter, Patricia

AU - Tan, Wei Shen

AU - Martínez-Fernández, Monica

AU - Paul, Dirk

AU - Hynes-Allen, Antony

AU - Rezaee, Sheida

AU - Gurung, Pratik

AU - Rodney, Simon

AU - Mehmood, Ahmed

AU - Villacampa, Felipe

AU - de la Rosa, Federico

AU - Jameson, Charles

AU - Cheng, Kar

AU - Zeegers, Maurice

AU - Bryan, Richard

AU - James, Nicholas

AU - Paramio, Jesus

AU - Freeman, Alex

AU - Beck, Stephan

AU - Kelly, John

PY - 2017/1/31

Y1 - 2017/1/31

N2 - BackgroundBladder 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.ResultsWe 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.ConclusionsEpigenetic 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.

AB - BackgroundBladder 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.ResultsWe 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.ConclusionsEpigenetic 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.

KW - Bladder cancer

KW - Epigenetics

KW - Urine

KW - Next generation sequencing

KW - Diagnostic

U2 - 10.1186/s13148-016-0303-5

DO - 10.1186/s13148-016-0303-5

M3 - Article

SN - 1868-7075

VL - 9

JO - Clinical epigenetics

JF - Clinical epigenetics

M1 - 8

ER -

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

Abstract

Keywords

UN SDGs

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Research output

Liquid biopsies for bladder cancer

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