A Panel of Plasma Exosomal miRNAs as Potential Biomarkers for Differential Diagnosis of Thyroid Nodules
A Panel of Plasma Exosomal miRNAs as Potential Biomarkers for Differential Diagnosis of Thyroid Nodules
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DOI：
10.3389/fgene.2020.00449
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发表时间：
2020-05-19
影响因子：
3.7
通讯作者：
Huang, Xiaoyi
中科院分区：
文献类型：
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作者：
Liang, Meihua;Yu, Siming;Huang, Xiaoyi
背景：使用循环胞外遗传物质的液体活检为甲状腺癌的诊断提供了新的见解。本研究旨在寻找可用于早期诊断甲状腺乳头状癌(PTC)的血浆来源的胞外体生物标志物。方法：分离良性甲状腺结节和PTC患者血浆中胞外体miRNAs。使用RNA测序(RNA-SEQ)对外体miRNA进行分析，以确定候选miRNA并区分良恶性。验证队列包括30名良性甲状腺结节患者、35名PTC患者和31名健康人。实时定量聚合酶链式反应(Real-Time-PCR)定量检测miRNA候选基因的表达。结果：通过RNA-SEQ，筛选出8个血浆外体miRNAs。进一步验证表明结节中miR-16-2-3p、miR-223-5p、miR-34c-5p、miR-182-5p、miR-223-3p和miR-146b-5p的表达水平显著低于正常对照组(p<；0.0001)，而miR-16-2-3p和miR-223-5p的表达水平显著高于良性结节(p<；0.05)。ROC分析表明，上述6种miRNAs是检测甲状腺结节的有效指标。同时，miR-16-2-3p和miR-223-5p可用于良性结节的PTC检测。结论：6种异常表达的血浆外体miRNAs可作为甲状腺结节与健康个体鉴别诊断的生物标志物。由miR-16-2-3p、miR-223-5p、miR-101-3p和miR-34c-5p组成的鉴定板具有鉴别甲状腺结节良恶性的条件。
Background: A liquid biopsy using circulating exosomal genetic materials provides new insights for thyroid cancer diagnosis. This study aimed to identify plasma-derived exosomal biomarkers that could be used for early detection of papillary thyroid carcinoma (PTC).Method: Exosomal miRNAs in plasma were isolated from patients with benign thyroid nodules and patients with PTC. Profiling of exosomal miRNA was performed using RNA sequencing (RNA-seq) to identify miRNA candidates and differentiate the benign from malignant. The validation cohort consisted of 30 patients with benign thyroid nodules, 35 PTC patients, and 31 healthy individuals. Real-time PCR was used to quantify the expression of miRNA candidates. The diagnostic potential of the candidates was evaluated by receiver operating characteristic (ROC) curves.Results: After RNA-seq, eight plasma exosomal miRNAs were selected as candidates. Further validation indicated that the levels of exosomal miR-16-2-3p, miR-223-5p, miR-34c-5p, miR-182-5p, miR-223-3p, and miR-146b-5p were significantly lower in nodules compared to healthy controls (p < 0.0001), whereas miR-16-2-3p and miR-223-5p were significantly higher in the PTC cases than in those with benign nodules (p < 0.05). ROC analyses revealed that the above six miRNAs were potent indicators for detection of thyroid nodules. Meanwhile, miR-16-2-3p and miR-223-5p can be utilized for detecting PTC from benign nodules. Additionally, combined miRNA panels showed increased diagnostic sensitivities and specificities compared to single miRNA markers.Conclusion: Six aberrantly expressed plasma exosomal miRNAs may be used as diagnostic biomarkers to differentiate thyroid nodules from healthy individuals. The panel consisting of miR-16-2-3p, miR-223-5p, miR-101-3p, and miR-34c-5p are eligible for discriminating benign from malignant thyroid nodules.