Feber Andrew, Dhami Pawan, Dong Liqin, de Winter Patricia, Tan Wei Shen, Martínez-Fernández Mónica, Paul Dirk S, Hynes-Allen Antony, Rezaee Sheida, Gurung Pratik, Rodney Simon, Mehmood Ahmed, Villacampa Felipe, de la Rosa Federico, Jameson Charles, Cheng Kar Keung, Zeegers Maurice P, Bryan Richard T, James Nicholas D, Paramio Jesus M, Freeman Alex, Beck Stephan, Kelly John D
UCL Cancer Institute, University College London, London, UK.
Division of Surgery & Interventional Science, UCL Medical School, University College London, London, UK.
Clin Epigenetics. 2017 Jan 31;9:8. doi: 10.1186/s13148-016-0303-5. eCollection 2017.
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 ( = 274, non-cancer ( = 167) and bladder cancer ( = 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.
膀胱癌（BC）是西方世界最常见的癌症之一，由于需要进行膀胱镜检查，其治疗费用也是最高的。膀胱癌常出现DNA甲基化变化，多项研究表明，通过检测晨尿中的表观遗传改变，尿液生物标志物具有潜在应用价值。本研究的目的是开发一种靶向亚硫酸氢盐新一代测序检测方法，以高灵敏度和特异性从尿液中诊断膀胱癌。
我们从86例肌肉浸润性膀胱癌和30例正常尿路上皮样本中确定了一个包含150个CpG位点的生物标志物panel。基于该panel，我们开发了UroMark检测方法，这是一种用于从尿沉渣DNA中检测膀胱癌的新一代亚硫酸氢盐测序检测方法及分析流程。150个位点的UroMark检测方法在一个独立队列（n = 274，非癌症患者（n = 167）和膀胱癌患者（n = 107））的晨尿样本中得到验证，曲线下面积（AUC）为97%。将UroMark分类器检测原发性膀胱癌的灵敏度98%、特异性97%和阴性预测值97%与非膀胱癌尿液进行了比较。
用于检测膀胱癌的表观遗传尿液生物标志物有可能彻底改变该疾病的管理方式。在这项概念验证研究中，我们展示了一种新型的基于高通量新一代测序的生物标志物的开发及其在检测尿液中膀胱癌特异性表观遗传改变方面的应用。
Zotero 插件
