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胶质母细胞瘤患者血清 miRNA 分析:基于 CD44 的细胞外囊泡富集可提高预后特征的特异性。

Analysis of Serum miRNA in Glioblastoma Patients: CD44-Based Enrichment of Extracellular Vesicles Enhances Specificity for the Prognostic Signature.

机构信息

Institute of Clinical Chemistry and Clinical Pharmacology, University of Bonn, 53127 Bonn, Germany.

Division of Clinical Neurooncology, Department of Neurology, Center of Integrated Oncology Aachen-Bonn-Cologne-Düsseldorf, Partner Site Bonn, University Hospital Bonn, 53127 Bonn, Germany.

出版信息

Int J Mol Sci. 2020 Sep 29;21(19):7211. doi: 10.3390/ijms21197211.

DOI:10.3390/ijms21197211
PMID:33003586
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7583802/
Abstract

Glioblastoma is a devastating disease, for which biomarkers allowing a prediction of prognosis are urgently needed. microRNAs have been described as potentially valuable biomarkers in cancer. Here, we studied a panel of microRNAs in extracellular vesicles (EVs) from the serum of glioblastoma patients and evaluated their correlation with the prognosis of these patients. The levels of 15 microRNAs in EVs that were separated by size-exclusion chromatography were studied by quantitative real-time PCR, followed by CD44 immunoprecipitation (SEC + CD44), and compared with those from the total serum of glioblastoma patients ( = 55) and healthy volunteers ( = 10). Compared to total serum, we found evidence for the enrichment of miR-21-3p and miR-106a-5p and, conversely, lower levels of miR-15b-3p, in SEC + CD44 EVs. miR-15b-3p and miR-21-3p were upregulated in glioblastoma patients compared to healthy subjects. A significant correlation with survival of the patients was found for levels of miR-15b-3p in total serum and miR-15b-3p, miR-21-3p, miR-106a-5p, and miR-328-3p in SEC + CD44 EVs. Combining miR-15b-3p in serum or miR-106a-5p in SEC + CD44 EVs with any one of the other three microRNAs in SEC + CD44 EVs allowed for a prognostic stratification of glioblastoma patients. We have thus identified four microRNAs in glioblastoma patients whose levels, in combination, can predict the prognosis for these patients.

摘要

胶质母细胞瘤是一种毁灭性疾病,迫切需要能够预测预后的生物标志物。microRNAs 已被描述为癌症中具有潜在价值的生物标志物。在这里,我们研究了来自胶质母细胞瘤患者血清中的一组 microRNAs,评估了它们与这些患者预后的相关性。通过定量实时 PCR 研究了通过尺寸排阻色谱法分离的 EVs 中的 15 个 microRNAs 的水平,随后进行了 CD44 免疫沉淀(SEC + CD44),并与胶质母细胞瘤患者的总血清(= 55)和健康志愿者的总血清进行了比较(= 10)。与总血清相比,我们在 SEC + CD44 EVs 中发现了 miR-21-3p 和 miR-106a-5p 富集的证据,相反,miR-15b-3p 的水平较低。miR-15b-3p 和 miR-21-3p 在胶质母细胞瘤患者中上调与健康受试者相比。在总血清中 miR-15b-3p 和 SEC + CD44 EVs 中 miR-15b-3p、miR-21-3p、miR-106a-5p 和 miR-328-3p 的水平与患者的生存存在显著相关性。在血清中结合 miR-15b-3p 或 SEC + CD44 EVs 中的 miR-106a-5p 与 SEC + CD44 EVs 中的其他三种 microRNAs 中的任何一种结合,都可以对胶质母细胞瘤患者进行预后分层。因此,我们鉴定了胶质母细胞瘤患者中的四种 microRNAs,它们的水平结合起来可以预测这些患者的预后。

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