A Panel of Four miRNAs Accurately Differentiates Malignant from Benign Indeterminate Thyroid Lesions on Fine Needle Aspiration
A Panel of Four miRNAs Accurately Differentiates Malignant from Benign Indeterminate Thyroid Lesions on Fine Needle Aspiration
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DOI：
10.1158/1078-0432.ccr-11-2487
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发表时间：
2012-04-01
影响因子：
11.5
通讯作者：
Fahey, Thomas J., III
中科院分区：
文献类型：
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作者：
Keutgen, Xavier M.;Filicori, Filippo;Fahey, Thomas J., III
目的：细针穿刺（FNA）检查不确定的甲状腺病变约25%为恶性。因此，甲状腺半切除术或全切除术通常被提倡用于明确诊断。在这项研究中，我们分析了不确定的FNA样本中的miRNA表达，并确定其预后对最终病理diagnosis.Experimental Design的影响：一个预测模型，来自使用29个体外不确定的甲状腺病变FNA区分恶性和良性肿瘤在三级转诊中心，并验证了一个独立的一组72前瞻性收集的体内FNA样本。使用逆转录酶PCR测定miR-222、miR-328、miR-197、miR-21、miR-181 a和miR-146 b的表达水平。使用支持向量机（SVM）方法开发统计模型。结果：使用交叉验证初步估计具有四种miRNA（miR-222、miR-328、miR-197和miR-21）的SVM模型具有86%的预测准确度。当应用于72个独立的体内验证样本时，性能实际上优于预测，灵敏度为100%，特异性为86%，预测准确性为90%，区分恶性和良性不确定病变。当排除Hurthle细胞病变时，总体准确性提高到97%，灵敏度为100%，特异性为95%.Conclusions：本研究表明，miR-222，miR-328，miR-197和miR-21的表达结合在预测模型中可以准确区分FNA上的恶性和良性不确定甲状腺病变。这些发现表明，FNA miRNA分析可能是甲状腺结节患者管理算法的有用辅助手段。临床癌症研究; 18（7）; 2032-8。(C)2012年AACR。
Purpose: Indeterminate thyroid lesions on fine needle aspiration (FNA) harbor malignancy in about 25% of cases. Hemi- or total thyroidectomy has, therefore, been routinely advocated for definitive diagnosis. In this study, we analyzed miRNA expression in indeterminate FNA samples and determined its prognostic effects on final pathologic diagnosis.Experimental Design: A predictive model was derived using 29 ex vivo indeterminate thyroid lesions on FNA to differentiate malignant from benign tumors at a tertiary referral center and validated on an independent set of 72 prospectively collected in vivo FNA samples. Expression levels of miR-222, miR-328, miR-197, miR-21, miR-181a, and miR-146b were determined using reverse transcriptase PCR. A statistical model was developed using the support vector machine (SVM) approach.Results: A SVM model with four miRNAs (miR-222, miR-328, miR-197, and miR-21) was initially estimated to have 86% predictive accuracy using cross-validation. When applied to the 72 independent in vivo validation samples, performance was actually better than predicted with a sensitivity of 100% and specificity of 86%, for a predictive accuracy of 90% in differentiating malignant from benign indeterminate lesions. When Hurthle cell lesions were excluded, overall accuracy improved to 97% with 100% sensitivity and 95% specificity.Conclusions: This study shows that that the expression of miR-222, miR-328, miR-197, and miR-21 combined in a predictive model is accurate at differentiating malignant from benign indeterminate thyroid lesions on FNA. These findings suggest that FNA miRNA analysis could be a useful adjunct in the management algorithm of patients with thyroid nodules. Clin Cancer Res; 18(7); 2032-8. (C) 2012 AACR.