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血清外泌体 microRNAs 作为子宫内膜异位症潜在的循环生物标志物。

Serum Exosomal MicroRNAs as Potential Circulating Biomarkers for Endometriosis.

机构信息

Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, NO.107 Wenhuaxi Road, Jinan, Shandong 250012, China.

Cryomedicine Lab, Qilu Hospital of Shandong University, Jinan, China.

出版信息

Dis Markers. 2020 Jan 23;2020:2456340. doi: 10.1155/2020/2456340. eCollection 2020.

Abstract

BACKGROUND

A reliable noninvasive biomarker is not yet available for endometriosis diagnosis. Novel biomarkers for the diagnosis of endometriosis are urgently needed. The molecular constituents of exosomes, especially exosomal microRNAs (miRNAs), have considerable potential as novel biomarkers for clinical diagnosis. This study is aimed at exploring aberrant exosomal miRNA profiles by using miRNA microarray and at providing more accurate molecular biomarkers of endometriosis.

METHODS

Exosomes were isolated from the serum of patients with endometriosis and negative controls and identified by electron microscopy, nanoparticle tracking analysis, and Western blot. Exosomal miRNAs were profiled by miRNA microarrays. The expression of selective serum exosomal miRNA was validated by qRT-PCR. Receiver operating characteristic (ROC) curves were established to explore the diagnostic value of selective miRNAs. Finally, GO annotation and KEGG pathway enrichment analyses were used to display possible functions associated with the two miRNAs.

RESULTS

A total of 24 miRNAs showed differential levels of enrichment with < 0.05 and |log fold change| > 1 by miRNA microarrays. Among the six selective miRNAs (i.e., miR-134-5p, miR-197-5p, miR-22-3p, miR-320a, miR-494-3p, and miR-939-5p), qRT-PCR analysis revealed that miR-22-3p and miR-320a were significantly upregulated in serum exosomes from patients with endometriosis compared with negative individuals. ROC curve revealed that the serum exosomal miR-22-3p and miR-320a yielded the area under the curve values of 0.855 and 0.827, respectively.

CONCLUSION

Our results demonstrated that exosomal miR-22-3p and miR-320a were significantly increased in the sera of patients with endometriosis. The two miRNAs may be useful potential biomarkers for endometriosis diagnosis.

摘要

背景

目前还没有可靠的非侵入性生物标志物可用于子宫内膜异位症的诊断。因此,迫切需要新的生物标志物来诊断子宫内膜异位症。外泌体的分子成分,特别是外泌体 microRNAs(miRNAs),具有作为临床诊断新型生物标志物的巨大潜力。本研究旨在通过 miRNA 微阵列探索异常的外泌体 miRNA 谱,并为子宫内膜异位症提供更准确的分子生物标志物。

方法

通过电子显微镜、纳米颗粒跟踪分析和 Western blot 从子宫内膜异位症患者和阴性对照者的血清中分离外泌体并进行鉴定。通过 miRNA 微阵列分析外泌体 miRNA 谱。通过 qRT-PCR 验证选择性血清外泌体 miRNA 的表达。建立受试者工作特征(ROC)曲线以探索选择性 miRNA 的诊断价值。最后,GO 注释和 KEGG 通路富集分析用于显示与两种 miRNA 相关的可能功能。

结果

miRNA 微阵列显示共有 24 个 miRNA 的丰度存在差异,差异倍数绝对值 > 1 且 < 0.05。在六个选择性 miRNA(miR-134-5p、miR-197-5p、miR-22-3p、miR-320a、miR-494-3p 和 miR-939-5p)中,qRT-PCR 分析显示,与阴性个体相比,子宫内膜异位症患者血清外泌体中的 miR-22-3p 和 miR-320a 显著上调。ROC 曲线显示,血清外泌体 miR-22-3p 和 miR-320a 的曲线下面积分别为 0.855 和 0.827。

结论

本研究结果表明,子宫内膜异位症患者血清中外泌体 miR-22-3p 和 miR-320a 显著增加。这两种 miRNA 可能是子宫内膜异位症诊断的有用的潜在生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7773/7008302/89e2a6cb9a05/DM2020-2456340.001.jpg

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