Division of Surgery and Interventional Science, University College London, 74 Huntley Street, London WC1E 6AU, UK; Department of Urology, University College London Hospital at Westmoreland Street, 16-18 Westmoreland Street, London W1G 8PH, UK.
Fitzwilliam College, University of Cambridge, Storey's Way, Cambridge CB3 0DG, UK.
Cancer Treat Rev. 2018 May;66:56-63. doi: 10.1016/j.ctrv.2018.03.007. Epub 2018 Apr 17.
Blood-based biomarkers are a neglected resource in bladder cancer, where the mainstay of focus has been on urinary biomarkers. However, blood-based biomarkers are gaining popularity in other solid cancers, particularly circulating tumour cells (CTCs) and circulating nucleic acids. In this systematic review, we identify and discuss the diagnostic value of CTC, cell-free DNA and RNA based biomarkers in bladder cancer.
A MEDLINE/Pubmed systematic search was performed using the following keywords: (bladder cancer) AND (blood OR plasma OR serum) AND biomarker AND (DNA OR RNA OR cfDNA OR cell-free DNA OR RNA OR CTC). All studies including blood-based biomarkers based on DNA, RNA and CTCs were reviewed. Of the included studies, studies reporting sensitivity, specificity and/or AUC/ROC values were further described.
Systematic searched yielded 47 studies that were eligible, of which 21, 19 and 3 studies reported DNA, RNA and CTC biomarkers respectively. 15 of these studies included sensitivity, specificity and/or AUC/ROC values. Biomarkers sensitivity and specificity ranged widely at 2.4-97.6% and 43.3-100% respectively. Median number of patients recruited in the studies was 56 (IQR 41-90). Only 3 studies included an independent validation cohort. The highest sensitivity and specificity pairing achieved in the validation cohort was 80.0% and 89.1% respectively.
This systematic review provides a comprehensive overview of the blood-based CTC and nucleic acid biomarkers that have been investigated. An overlap in interest of targets between studies suggests that these could be promising biomarkers, but few biomarkers achieve high sensitivity and specificity, and fewer still have been validated independently.
在膀胱癌中,血液生物标志物是一个被忽视的资源,主要关注点一直集中在尿液生物标志物上。然而,血液生物标志物在其他实体瘤中越来越受欢迎,特别是循环肿瘤细胞(CTC)和循环核酸。在这项系统评价中,我们确定并讨论了 CTC、无细胞 DNA 和基于 RNA 的生物标志物在膀胱癌中的诊断价值。
使用以下关键词对 MEDLINE/Pubmed 系统进行了搜索:(膀胱癌)和(血液或血浆或血清)和生物标志物和(DNA 或 RNA 或 cfDNA 或无细胞 DNA 或 RNA 或 CTC)。综述了所有包含基于 DNA、RNA 和 CTC 的血液生物标志物的研究。在纳入的研究中,进一步描述了报告敏感性、特异性和/或 AUC/ROC 值的研究。
系统搜索产生了 47 项符合条件的研究,其中 21 项、19 项和 3 项研究分别报告了 DNA、RNA 和 CTC 生物标志物。其中 15 项研究包括敏感性、特异性和/或 AUC/ROC 值。生物标志物的敏感性和特异性范围很广,分别为 2.4-97.6%和 43.3-100%。研究中纳入的患者中位数为 56(IQR 41-90)。只有 3 项研究包括独立验证队列。在验证队列中获得的最高敏感性和特异性配对分别为 80.0%和 89.1%。
这项系统评价提供了对已研究的血液 CTC 和核酸生物标志物的全面概述。研究之间目标的兴趣重叠表明这些可能是有前途的生物标志物,但很少有生物标志物具有高敏感性和特异性,更少的生物标志物得到独立验证。