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

被引：87

作者：

Feber, Andrew ^{[1
]}

Dhami, Pawan ^{[1
]}

Dong, Liqin ^{[1
]}

de Winter, Patricia ^{[2
]}

Tan, Wei Shen ^{[2
]}

Martinez-Fernandez, Monica ^{[3
,4
]}

Paul, Dirk S. ^{[1
]}

Hynes-Allen, Antony ^{[2
]}

Rezaee, Sheida ^{[1
]}

Gurung, Pratik ^{[2
,6
]}

Rodney, Simon ^{[2
]}

Mehmood, Ahmed ^{[2
]}

Villacampa, Felipe ^{[10
,11
,12
]}

de la Rosa, Federico ^{[10
,11
,12
]}

Jameson, Charles ^{[5
]}

Cheng, Kar Keung ^{[7
]}

Zeegers, Maurice P. ^{[7
,8
]}

Bryan, Richard T. ^{[6
]}

James, Nicholas D. ^{[9
]}

Paramio, Jesus M. ^{[3
,4
,12
]}

Freeman, Alex ^{[5
]}

Beck, Stephan ^{[1
]}

Kelly, John D. ^{[1
,2
]}

机构：

[1] UCL, UCL Canc Inst, London, England

[2] UCL, UCL Med Sch, Div Surg & Intervent Sci, London, England

[3] CIEMAT Ed70A, Mol Oncol Unit, Madrid, Spain

[4] Univ Hosp 12 Octubre, Biomed Res Inst 1 12, Av Cordoba S-N, Madrid 28041, Spain

[5] Univ Coll London Hosp, Dept Histopathol, London, England

[6] Univ Birmingham, Sch Canc Sci, Birmingham, W Midlands, England

[7] Univ Birmingham, Inst Appl Hlth Res, Birmingham, W Midlands, England

[8] Maastricht Univ, Sch Publ Hlth & Primary Care, Maastricht, Netherlands

[9] Univ Warwick, Canc Res Unit, Coventry, W Midlands, England

[10] Univ Hosp 12 Octubre, Urooncol Sect, Av Cordoba S-N, Madrid 28041, Spain

[11] Univ Hosp 12 Octubre, Biomed Res Inst 1 12, Av Cordoba S-N, Madrid 28041, Spain

[12] Biomed Red Canc CIBER ONC, Ctr Invest, Madrid, Spain

来源：

CLINICAL EPIGENETICS | 2017年 / 9卷

基金：

欧盟第七框架计划; 英国惠康基金;

关键词：

Bladder cancer; Epigenetics; Urine; Next generation sequencing; Diagnostic; DNA METHYLATION; LARGE-SCALE; 5-AMINOLEVULINIC ACID; HEMATURIA; MARKERS; SURVEILLANCE; CYSTOSCOPY; RECURRENCE; MANAGEMENT; CARCINOMA;

D O I：

10.1186/s13148-016-0303-5

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页数：10

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