Zou Xuan, Gao Feng, Wang Zhi-Yan, Zhang Huo, Liu Qing-Xie, Jiang Lin, Zhou Xin, Zhu Wei
First Clinical College of Nanjing Medical University, Nanjing, Jiangsu 210029, China.
Department of Orthopedics, First Affiliated Hospital of Nanjing Medical University, Jiangsu 210029, China.
Chin Med J (Engl). 2020 Nov 5;133(21):2543-2551. doi: 10.1097/CM9.0000000000001107.
Accumulating evidence has revealed that circulating microRNAs (miRNAs) can serve as non-invasive biomarkers for cancer diagnosis. This study aimed to identify differentially expressed miRNAs in serum which might become potential biomarkers for non-invasive diagnosis of papillary thyroid carcinoma (PTC).
The experiment was carried out between 2015 and 2017. In the screening stage, the Exiqon miRNA quantitative real-time polymerase chain reaction (qPCR) panel was applied to select candidate miRNAs. In the following training, testing, and external validation stages, the serum samples of 100 patients and 96 healthy controls (HCs) were analyzed to compare the expression levels of the identified miRNAs. The areas under the receiver operating characteristic curves (AUCs) were calculated to assess the diagnostic value of the identified signature.
Three miRNAs (miR-25-3p, miR-296-5p, and miR-92a-3p) in serum were consistently up-regulated in PTC patients compared with HCs. A three-miRNA panel was constructed by logistic regression analysis and showed better diagnostic performance than a single miRNA for PTC detection. The AUCs of the panel were 0.727, 0.771, and 0.862 for the training, testing, and external validation stage, respectively. Meanwhile, the panel showed stable capability in differentiating PTC patients from patients with benign goiters, with an AUC as high as 0.969. For further exploration, the three identified miRNAs were analyzed in tissue samples (23 PTC vs. 23 HCs) and serum-derived exosomes samples (24 PTC vs. 24 HCs), and the altered expression in the tumor also indicated their close relationship with PTC disease.
We identify a three-miRNA panel in serum which might serve as a promising biomarker for PTC diagnosis.
越来越多的证据表明，循环微RNA（miRNA）可作为癌症诊断的非侵入性生物标志物。本研究旨在鉴定血清中差异表达的miRNA，其可能成为甲状腺乳头状癌（PTC）非侵入性诊断的潜在生物标志物。
实验于2015年至2017年进行。在筛选阶段，应用Exiqon miRNA定量实时聚合酶链反应（qPCR）检测板筛选候选miRNA。在随后的训练、测试和外部验证阶段，分析100例患者和96例健康对照（HC）的血清样本，比较所鉴定miRNA的表达水平。计算受试者工作特征曲线（AUC）下的面积，以评估所鉴定标志物的诊断价值。
与HC相比，PTC患者血清中的三种miRNA（miR-25-3p、miR-296-5p和miR-92a-3p）持续上调。通过逻辑回归分析构建了一个三miRNA检测板，其在检测PTC方面显示出比单个miRNA更好的诊断性能。该检测板在训练、测试和外部验证阶段的AUC分别为0.727、0.771和0.862。同时，该检测板在区分PTC患者和良性甲状腺肿患者方面表现出稳定的能力，AUC高达0.969。为进一步探索，在组织样本（23例PTC与23例HC）和血清来源的外泌体样本（24例PTC与24例HC）中分析了所鉴定的三种miRNA，肿瘤中表达的改变也表明它们与PTC疾病密切相关。
我们在血清中鉴定出一个三miRNA检测板，其可能成为PTC诊断的有前景的生物标志物。
