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TPO(+) 细胞外囊泡来源的 miRNA let-7 是滤泡性甲状腺结节鉴别诊断的潜在标志物。

MiRNA let-7 from TPO(+) Extracellular Vesicles is a Potential Marker for a Differential Diagnosis of Follicular Thyroid Nodules.

机构信息

Subcellular Technology Lab., N.N. Petrov National Medical Research Center of Oncology, 195251 St. Petersburg, Russia.

Oncosystem Ltd., 121205 Moscow, Russia.

出版信息

Cells. 2020 Aug 18;9(8):1917. doi: 10.3390/cells9081917.

Abstract

BACKGROUND

The current approaches to distinguish follicular adenomas (FA) and follicular thyroid cancer (FTC) at the pre-operative stage have low predictive value. Liquid biopsy-based analysis of circulating extracellular vesicles (EVs) presents a promising diagnostic method. However, the extreme heterogeneity of plasma EV population hampers the development of new diagnostic tests. We hypothesize that the isolation of EVs with thyroid-specific surface molecules followed by miRNA analysis, may have improved diagnostic potency.

METHODS

The total population of EVs was isolated from the plasma of patients with FA ( = 30) and FTC ( = 30). Thyroid peroxidase (TPO)-positive EVs were isolated from the total populations using immune-beads. The miRNA from the TPO(+)EVs obtained from the plasma of FA and FTC patients was assayed by RT-PCR. The diagnostic potency of the selected miRNAs was estimated by the receiver operating characteristic (ROC) analysis.

RESULTS

TPO(+)EVs can be efficiently isolated by immunobeads. The analysis of Let-7 family members in TPO(+)EVs allows one to distinguish FA and FTC with high accuracy (area under curve defined by ROC = 0.77-0.84).

CONCLUSION

The isolation of TPO(+)EVs, followed by RT-qPCR analysis of Let-7 family members, may present a helpful approach to manage follicular nodules in the thyroid gland.

摘要

背景

目前在术前阶段区分滤泡性腺瘤(FA)和滤泡性甲状腺癌(FTC)的方法预测价值较低。基于液体活检的循环细胞外囊泡(EVs)分析提供了一种很有前途的诊断方法。然而,血浆 EV 群体的极端异质性阻碍了新诊断测试的发展。我们假设,使用甲状腺特异性表面分子分离 EVs 并进行 miRNA 分析,可能会提高诊断效力。

方法

从 FA(n=30)和 FTC(n=30)患者的血浆中分离总 EV 群体。使用免疫珠从总群体中分离甲状腺过氧化物酶(TPO)阳性 EVs。使用 RT-PCR 测定从 FA 和 FTC 患者血浆中获得的 TPO(+)EVs 的 miRNA。通过接收者操作特征(ROC)分析估计选定 miRNA 的诊断效力。

结果

TPO(+)EVs 可通过免疫珠高效分离。TPO(+)EVs 中 Let-7 家族成员的分析可以高精度区分 FA 和 FTC(ROC 定义的曲线下面积为 0.77-0.84)。

结论

TPO(+)EV 的分离,以及随后对 Let-7 家族成员的 RT-qPCR 分析,可能为甲状腺滤泡结节的管理提供一种有用的方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0099/7465637/8b48b6a546aa/cells-09-01917-g001.jpg

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