Prognostic DNA methylation markers for sporadic colorectal cancer: a systematic review.
Prognostic DNA methylation markers for sporadic colorectal cancer: a systematic review.
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DOI：
10.1186/s13148-018-0461-8
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发表时间：
2018
影响因子：
5.7
通讯作者：
Smits KM
中科院分区：
文献类型：
--
作者：
Draht MXG;Goudkade D;Koch A;Grabsch HI;Weijenberg MP;van Engeland M;Melotte V;Smits KM
为了更好地管理结直肠癌，迫切需要能够预测结直肠癌（CRC）患者预后并能够将高风险早期患者与低风险早期患者分层的生物标志物。在过去的几十年中，大量的各种预后DNA甲基化标记物已在文献中发表。然而，迄今为止，这些标记物都没有用于临床实践。为了获得已发表的CRC预后甲基化标志物的数量、独立验证的标志物数量以及当前证据水平（LoE）的概述，我们对PubMed、EMBASE和MEDLINE进行了系统综述。此外，我们根据REMARK指南对研究进行评分，该指南旨在提高预后生物标志物研究的透明度和完整报告。83项研究报告了123种甲基化标志物，符合研究入选标准，并根据REMARK进行评分。63项研究调查了单一甲基化标记物，而20项研究报告了甲基化标记物的组合。我们观察到关于样本量和患者特征、统计分析和方法的报告存在实质性差异。研究的中位（范围）REMARK评分为10.7分（4.5 - 17.5），最多20分。报告p值低于0.05的研究中的中位REMARK评分低于未报告p值的研究（p = 0.005）。观察到生存分析报告的p值与研究人群规模之间存在临界统计学显著相关性（p = 0.051）。在123个标记物中，只有23个（17%）在两个或多个研究系列中进行了研究。对于12种标记物和两种多标记物组，在两个或多个研究系列中报告了一致的结果。对于四种标记物，目前的LoE为II级，对于所有其他标记物，LoE较低。这项系统性综述反映了大多数CRC甲基化标志物研究中缺乏根据REMARK的充分报告和预后甲基化标志物的验证。然而，这篇系统性综述对已发表的CRC预后甲基化标志物进行了全面概述，并强调了过去二十年中发表的最有前途的标志物。本文的在线版本（10.1186/s13148-018-0461-8）包含补充材料，可供授权用户使用。
Biomarkers that can predict the prognosis of colorectal cancer (CRC) patients and that can stratify high-risk early stage patients from low-risk early stage patients are urgently needed for better management of CRC. During the last decades, a large variety of prognostic DNA methylation markers has been published in the literature. However, to date, none of these markers are used in clinical practice. To obtain an overview of the number of published prognostic methylation markers for CRC, the number of markers that was validated independently, and the current level of evidence (LoE), we conducted a systematic review of PubMed, EMBASE, and MEDLINE. In addition, we scored studies based on the REMARK guidelines that were established in order to attain more transparency and complete reporting of prognostic biomarker studies. Eighty-three studies reporting on 123 methylation markers fulfilled the study entry criteria and were scored according to REMARK. Sixty-three studies investigated single methylation markers, whereas 20 studies reported combinations of methylation markers. We observed substantial variation regarding the reporting of sample sizes and patient characteristics, statistical analyses, and methodology. The median (range) REMARK score for the studies was 10.7 points (4.5 to 17.5) out of a maximum of 20 possible points. The median REMARK score was lower in studies, which reported a p value below 0.05 versus those, which did not (p = 0.005). A borderline statistically significant association was observed between the reported p value of the survival analysis and the size of the study population (p = 0.051). Only 23 out of 123 markers (17%) were investigated in two or more study series. For 12 markers, and two multimarker panels, consistent results were reported in two or more study series. For four markers, the current LoE is level II, for all other markers, the LoE is lower. This systematic review reflects that adequate reporting according to REMARK and validation of prognostic methylation markers is absent in the majority of CRC methylation marker studies. However, this systematic review provides a comprehensive overview of published prognostic methylation markers for CRC and highlights the most promising markers that have been published in the last two decades. The online version of this article (10.1186/s13148-018-0461-8) contains supplementary material, which is available to authorized users.
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影响因子：
29.4
作者：
Boland CR;Goel A
通讯作者：
Goel A
影响因子：
8.8
作者：
Cui T;Chen Y;Yang L;Knösel T;Zöller K;Huber O;Petersen I
通讯作者：
Petersen I
影响因子：
--
作者：
Abdelmaksoud-Dammak, Rania;Miladi-Abdennadher, Imen;Mokdad-Gargouri, Raja
通讯作者：
Mokdad-Gargouri, Raja
影响因子：
24.5
作者：
Church TR;Wandell M;Lofton-Day C;Mongin SJ;Burger M;Payne SR;Castaños-Vélez E;Blumenstein BA;Rösch T;Osborn N;Snover D;Day RW;Ransohoff DF;PRESEPT Clinical Study Steering Committee, Investigators and Study Team
通讯作者：
PRESEPT Clinical Study Steering Committee, Investigators and Study Team
影响因子：
3.8
作者：
Dallol, Ashraf;Al-Maghrabi, Jaudah;Al-Qahtani, Mohammed H.
通讯作者：
Al-Qahtani, Mohammed H.