MicroRNA expression profiling of thyroid tumors: Biological significance and diagnostic utility
MicroRNA expression profiling of thyroid tumors: Biological significance and diagnostic utility
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DOI：
10.1210/jc.2007-2696
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发表时间：
2008-05-01
影响因子：
5.8
通讯作者：
Nikiforov, Yuri E.
中科院分区：
文献类型：
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作者：
Nikiforova, Marina N.;Tseng, George C.;Nikiforov, Yuri E.
目的：microRNA（miRNA）在多种肿瘤中表达失调。我们试图研究miRNA在所有主要类型的甲状腺肿瘤中的表达模式，包括携带不同致癌突变的肿瘤，并探索miRNA谱在甲状腺结节术前诊断中的实用性。设计：在60例手术切除的甲状腺肿瘤和非肿瘤样本以及62例细针穿刺（FNA）样本中，通过RT-PCR检测了miRNA表达水平。使用TaqMan MicroRNA Panel或单个miRNA序列特异性引物进行PCR。计算相对于正常甲状腺组织的miRNA表达水平。所有肿瘤的基因型最常见的mutations.Results：各种组织病理类型的甲状腺肿瘤，包括那些来自相同的细胞类型，表现出显着不同的配置文件的miRNA表达。嗜酸细胞肿瘤、传统滤泡性肿瘤、乳头状癌和髓样癌在无监督分层聚类分析中形成了不同的聚类。在乳头状癌中观察到miRNA表达模式与体细胞突变之间的显著相关性。一组七种miRNAs在FNA样本中验证了在甲状腺肿瘤与手术样本中的增生结节中最差异过表达的miR-187、miR-221、miR-222、miR-146 b、miR-155、miR-224和miR-197，显示了甲状腺癌检测的高准确性。在这项研究中，我们证明了不同组织病理学类型的甲状腺肿瘤具有不同的miRNA谱，在相同的肿瘤类型中进一步不同，反映了特定的致癌突变。一组有限的miRNAs可以高准确度地用于诊断，以检测手术和术前FNA样本中的甲状腺癌。
Objective: MicroRNA (miRNA) expression is deregulated in many types of human cancers. We sought to investigate the expression patterns of miRNA in all major types of thyroid tumors, including tumors carrying distinct oncogenic mutations, and to explore the utility of miRNA profiling for the preoperative diagnosis of thyroid nodules.Design: miRNA expression levels were detected in 60 surgically removed thyroid neoplastic and nonneoplastic samples and in 62 fine-needle aspiration (FNA) samples by RT-PCR using TaqMan MicroRNA Panel or individual miRNA sequence-specific primers. miRNA expression levels were calculated relative to normal thyroid tissue. All tumors were genotyped for most common mutations.Results: Various histopathological types of thyroid tumors, including those deriving from the same cell type, showed significantly different profiles of miRNA expression. Oncocytic tumors, conventional follicular tumors, papillary carcinomas, and medullary carcinomas formed distinct clusterson the unsupervised hierarchical clustering analysis. Significant correlation between miRNA expression patterns and somatic mutations was observed in papillary carcinomas. A set of seven miRNAs (miR-187, miR-221, miR-222, miR-146b, miR-155, miR-224, and miR-197) that were most differentially overexpressed in thyroid tumors vs. hyperplastic nodules in the surgical samples was validated in the FNA samples, showing high accuracy of thyroid cancer detection.Conclusions: In this study, we demonstrate that various histopathological types of thyroid tumors have distinct miRNA profiles, which further differ within the same tumor type, reflecting specific oncogenic mutations. A limited set of miRNAs can be used diagnostically with high accuracy to detect thyroid cancer in the surgical and preoperative FNA samples.