UroMark-a urinary biomarker assay for the detection of bladder cancer.
UroMark-a urinary biomarker assay for the detection of bladder cancer.
复制标题
乌马克-A尿生物标志物测定用于检测膀胱癌。
DOI：
10.1186/s13148-016-0303-5
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发表时间：
2017
影响因子：
5.7
通讯作者：
Kelly JD
中科院分区：
文献类型：
--
作者：
Feber A;Dhami P;Dong L;de Winter P;Tan WS;Martínez-Fernández M;Paul DS;Hynes-Allen A;Rezaee S;Gurung P;Rodney S;Mehmood A;Villacampa F;de la Rosa F;Jameson C;Cheng KK;Zeegers MP;Bryan RT;James ND;Paramio JM;Freeman A;Beck S;Kelly JD
膀胱癌（BC）是西方世界最常见的癌症之一，由于需要膀胱镜检查，因此是最昂贵的管理。BC显示DNA甲基化的频繁变化，并且一些研究已经通过检测排尿中的表观遗传改变显示了尿生物标志物的潜在效用。本研究的目的是开发一种具有高灵敏度和特异性的靶向亚硫酸氢盐下一代测序检测方法，以诊断尿液中的BC。我们从86例肌层浸润性膀胱癌和30例正常尿路上皮中确定了150个CpG位点的生物标志物组。基于此，我们开发了UroMark检测试剂盒，这是一种新一代亚硫酸氢盐测序检测试剂盒和分析管道，用于从尿沉渣DNA中检测膀胱癌。在一个独立队列（n = 274，非癌症（n = 167）和膀胱癌（n = 107））排泄尿液样本中验证了150个位点UroMark测定，AUC为97%。UroMark分类器检测原发性BC的灵敏度为98%，特异性为97%，NPV为97%，与非BC尿液进行了比较。用于检测BC的表观遗传尿液生物标志物有可能彻底改变这种疾病的管理。在这项概念验证研究中，我们展示了一种新的高通量、下一代基于测序的生物标志物的开发和实用性，用于检测尿液中BC特异性表观遗传学改变。本文的在线版本（doi：10.1186/s13148-016-0303-5）包含补充材料，可供授权用户使用。
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. The online version of this article (doi:10.1186/s13148-016-0303-5) contains supplementary material, which is available to authorized users.