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miRNA 之幻:我们距离找到子宫内膜异位症的非侵入性诊断生物标志物还有多远?系统综述。

The miRNA Mirage: How Close Are We to Finding a Non-Invasive Diagnostic Biomarker in Endometriosis? A Systematic Review.

机构信息

Endometriosis CaRe Centre, Nuffield Department of Women's and Reproductive Health, University of Oxford, Oxford OX1 2JD, UK;.

Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX1 2JD, UK.

出版信息

Int J Mol Sci. 2018 Feb 17;19(2):599. doi: 10.3390/ijms19020599.


DOI:10.3390/ijms19020599
PMID:29463003
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5855821/
Abstract

BACKGROUND: Endometriosis is a common disorder of the reproductive age group, characterised by the presence of ectopic endometrial tissue. The disease not only causes enormous suffering to the affected women, but also brings a tremendous medical and economic burden to bear on society. There is a long lag phase between the onset and diagnosis of the disease, mainly due to its non-specific symptoms and the lack of a non-invasive test. Endometriosis can only be diagnosed invasively by laparoscopy. A specific, non-invasive test to diagnose endometriosis is an unmet clinical need. The recent discovery of microRNAs (miRNAs) as modulators of gene expression, and their stability and specificity, make them an attractive candidate biomarker. Various studies on miRNAs in endometriosis have identified their cardinal role in the pathogenesis of the disease, and have proposed them as potential biomarkers in endometriosis. Rationale/Objectives: The aims of this review were to study the role of circulatory miRNAs in endometriosis, and bring to light whether circulatory miRNAs could be potential non-invasive biomarkers to diagnose the disease. SEARCH METHODS: Three databases, PubMed, EMBASE, and BIOSIS were searched, using a combination of Mesh or Emtree headings and free-text terms, to identify literature relating to circulating miRNAs in endometriosis published from 1996 to 31 December 2017. Only peer-reviewed, full-text original research articles in English were included in the current review. The studies meeting the inclusion criteria were critically assessed and checked using the QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies) tool. The dysregulated miRNAs were assessed regarding the concordance between the various studies and their role in the disease. OUTCOMES: Nine studies were critically analysed, and 42 different miRNAs were found to be dysregulated in them, with only one common miRNA (miR-20a) differentially expressed in more than one study. miR-17-5p/20a, miR-200, miR-199a, miR-143, and miR-145 were explored for their pivotal role in the aetiopathogenesis of endometriosis. Wider implications: It is emerging that miRNAs play a central role in the pathogenesis of endometriosis and have the potential of being promising biomarkers. Circulating miRNAs as a non-invasive diagnostic tool may shorten the delay in the diagnosis of the disease, thus alleviating the suffering of women and reducing the burden on health care systems. However, despite numerous studies on circulating miRNAs in endometriosis, no single miRNA or any panel of them seems to meet the criteria of a diagnostic biomarker. The disagreement between the various studies upholds the demand of larger, well-controlled systematic validation studies with uniformity in the research approaches and involving diverse populations.

摘要

背景:子宫内膜异位症是一种常见的生殖年龄组疾病,其特征是存在异位子宫内膜组织。这种疾病不仅给受影响的妇女带来了巨大的痛苦,而且还给社会带来了巨大的医疗和经济负担。疾病的发病和诊断之间存在很长的潜伏期,主要是由于其非特异性症状和缺乏非侵入性测试。子宫内膜异位症只能通过腹腔镜检查进行诊断。诊断子宫内膜异位症的特异性、非侵入性测试是临床未满足的需求。最近发现 microRNAs (miRNAs) 作为基因表达的调节剂,以及它们的稳定性和特异性,使它们成为有吸引力的候选生物标志物。各种关于子宫内膜异位症中 miRNAs 的研究已经确定了它们在疾病发病机制中的核心作用,并提出了它们作为子宫内膜异位症潜在生物标志物的可能性。

目的:本综述的目的是研究循环 miRNAs 在子宫内膜异位症中的作用,并阐明循环 miRNAs 是否可以成为诊断该疾病的潜在非侵入性生物标志物。

检索方法:使用 Mesh 或 Emtree 标题和自由文本术语的组合,在 PubMed、EMBASE 和 BIOSIS 三个数据库中进行搜索,以确定 1996 年至 2017 年 12 月 31 日期间发表的与子宫内膜异位症中循环 miRNAs 相关的文献。仅纳入符合条件的同行评议、全文原始研究文章。使用 QUADAS-2(诊断准确性研究质量评估工具)工具对符合纳入标准的研究进行严格评估和检查。评估失调的 miRNAs,以了解它们在各种研究之间的一致性及其在疾病中的作用。

结果:对 9 项研究进行了批判性分析,发现 42 种不同的 miRNAs 失调,只有一种常见的 miRNA(miR-20a)在一项以上的研究中差异表达。miR-17-5p/20a、miR-200、miR-199a、miR-143 和 miR-145 被探索用于其在子宫内膜异位症发病机制中的关键作用。

更广泛的意义:miRNAs 在子宫内膜异位症的发病机制中起着核心作用,并且具有成为有前途的生物标志物的潜力。作为一种非侵入性诊断工具的循环 miRNAs 可能会缩短疾病诊断的延迟,从而减轻妇女的痛苦并减轻医疗保健系统的负担。然而,尽管有许多关于子宫内膜异位症中循环 miRNAs 的研究,但似乎没有一种 miRNA 或任何一组 miRNA 符合诊断生物标志物的标准。各种研究之间的分歧支持需要进行更大规模、更好控制的系统验证研究,研究方法统一,并涉及不同人群。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8440/5855821/1a2aa88d486f/ijms-19-00599-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8440/5855821/f47c1c8ca989/ijms-19-00599-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8440/5855821/3276091016dc/ijms-19-00599-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8440/5855821/9e293e8349cf/ijms-19-00599-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8440/5855821/24c1502695a9/ijms-19-00599-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8440/5855821/ef2af6a274bf/ijms-19-00599-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8440/5855821/1a2aa88d486f/ijms-19-00599-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8440/5855821/f47c1c8ca989/ijms-19-00599-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8440/5855821/3276091016dc/ijms-19-00599-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8440/5855821/9e293e8349cf/ijms-19-00599-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8440/5855821/24c1502695a9/ijms-19-00599-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8440/5855821/ef2af6a274bf/ijms-19-00599-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8440/5855821/1a2aa88d486f/ijms-19-00599-g006.jpg

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miR-31 and miR-145 as Potential Non-Invasive Regulatory Biomarkers in Patients with Endometriosis.

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