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UroMark—a urinary biomarker assay for the detection of bladder cancer
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(2017) UroMark—a urinary biomarker assay for the detection of bladder cancer. Clinical Epigenetics, 9 (1). 8. doi:10.1186/s13148-016-0303-5 ISSN 1868-7075.
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WRAP-UroMark-urinary-biomarker-assay-James-2017.pdf - Published Version - Requires a PDF viewer. Available under License Creative Commons Attribution 4.0. Download (3519Kb) | Preview |
Official URL: http://dx.doi.org/10.1186/s13148-016-0303-5
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.
Item Type: | Journal Article | ||||||||||||||||||||||||
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Subjects: | R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer) | ||||||||||||||||||||||||
Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Health Sciences > Cancer Research Unit Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Health Sciences Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School |
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Library of Congress Subject Headings (LCSH): | Bladder -- Cancer, Urine -- Analysis, Proteomics -- Methodology, Biochemical markers | ||||||||||||||||||||||||
Journal or Publication Title: | Clinical Epigenetics | ||||||||||||||||||||||||
Publisher: | BioMed Central Ltd. | ||||||||||||||||||||||||
ISSN: | 1868-7075 | ||||||||||||||||||||||||
Official Date: | 31 January 2017 | ||||||||||||||||||||||||
Dates: |
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Volume: | 9 | ||||||||||||||||||||||||
Number: | 1 | ||||||||||||||||||||||||
Article Number: | 8 | ||||||||||||||||||||||||
DOI: | 10.1186/s13148-016-0303-5 | ||||||||||||||||||||||||
Status: | Peer Reviewed | ||||||||||||||||||||||||
Publication Status: | Published | ||||||||||||||||||||||||
Access rights to Published version: | Open Access (Creative Commons) | ||||||||||||||||||||||||
Date of first compliant deposit: | 26 September 2017 | ||||||||||||||||||||||||
Date of first compliant Open Access: | 2 October 2017 | ||||||||||||||||||||||||
Funder: | Medical Research Council (Great Britain) (MRC), Seventh Framework Programme (European Commission) (FP7), Wellcome Trust (London, England), Comunità Autonoma di Madrid, Urology Foundation, Advanced Encryption Standard | ||||||||||||||||||||||||
Grant number: | (MR/M025411/1, 282510, (99148, ISCIII-RETIC RD12/0036/0009, SAF2012-34378 and SAF2015-66015-R, FEDER | ||||||||||||||||||||||||
RIOXX Funder/Project Grant: |
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