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发育异常的巴雷特食管生物标志物:准备好进入黄金时代了吗?

Biomarkers for dysplastic Barrett's: ready for prime time?

作者信息

Gregson Eleanor M, Fitzgerald Rebecca C

机构信息

MRC Cancer Unit, Hutchison/MRC Research Centre, University of Cambridge, Biomedical Campus, Box 197, Cambridge, CB2 0XZ, UK,

出版信息

World J Surg. 2015 Mar;39(3):568-77. doi: 10.1007/s00268-014-2640-x.

Abstract

BACKGROUND

There is need for the application of biomarkers in a clinical setting in order to improve patient care. Current surveillance methods are costly for health care systems and invasive for patients, and subjective methodology leads to frequent misdiagnosis. This review summarises the most advanced recent and relevant literature in the field of biomarker development in the context of Barrett's esophagus and comments on their potential application. Studies included roughly correlate with Early Detection Research Network phases three and four.

RECENT FINDINGS

A number of individual candidate and panels of biomarkers have been investigated recently. These include: gene-specific mutations such as loss of heterozygosity, copy number alterations (in particular aneuploidy) methylation panels, altered gene expression, and glycosylation assayed by lectin binding, as well as genetic and clonal diversity measures. Immunostaining for p53 is the only candidate biomarker deemed "ready for prime time." This has been recommended for use clinically as an adjunct to histological diagnosis of dysplastic Barrett's esophagus in the 2014 British Society of Gastroenterology guidelines on the diagnosis and management of Barrett's esophagus.

CONCLUSIONS

Progress is being made but in many cases further prospective validation studies are required before clinical application can take place. Limitations to furthering these studies include the large patient cohorts required for prospective validation studies, costs associated with studies, and reproducibility of methods across laboratories. Continued research in this area is strongly recommended as, in the long run, biomarker application has the potential to significantly improve patient care.

摘要

背景

为改善患者护理,需要在临床环境中应用生物标志物。当前的监测方法对医疗保健系统成本高昂,对患者具有侵入性,且主观方法导致频繁误诊。本综述总结了巴雷特食管领域生物标志物开发方面最新的相关先进文献,并对其潜在应用进行了评论。纳入的研究大致与早期检测研究网络的三、四阶段相关。

最新发现

最近已经对许多单个候选生物标志物和生物标志物组合进行了研究。这些包括:基因特异性突变,如杂合性缺失、拷贝数改变(特别是非整倍体)、甲基化组合、基因表达改变、通过凝集素结合测定的糖基化,以及遗传和克隆多样性测量。p53免疫染色是唯一被认为“已准备好投入实际应用”的候选生物标志物。在2014年英国胃肠病学会关于巴雷特食管诊断和管理的指南中,已建议将其作为发育异常巴雷特食管组织学诊断的辅助手段在临床中使用。

结论

正在取得进展,但在许多情况下,在临床应用之前还需要进一步的前瞻性验证研究。推进这些研究的限制包括前瞻性验证研究所需的大量患者队列、研究相关成本以及各实验室方法的可重复性。强烈建议在该领域持续开展研究,因为从长远来看,生物标志物的应用有可能显著改善患者护理。

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