MicroRNA profile of poorly differentiated thyroid carcinomas: new diagnostic and prognostic insights.
MicroRNA profile of poorly differentiated thyroid carcinomas: new diagnostic and prognostic insights.
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DOI：
10.1530/jme-13-0266
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发表时间：
2014-04
影响因子：
3.5
通讯作者：
Nikiforova MN
中科院分区：
文献类型：
--
作者：
Dettmer MS;Perren A;Moch H;Komminoth P;Nikiforov YE;Nikiforova MN
普通型和嗜酸性低分化甲状腺癌的诊断是困难的。本研究的目的是确定它们的miRNA表达谱，并将其与分化良好的甲状腺肿瘤进行比较，以及识别可能作为诊断和预后标志物的miRNAs。应用聚合酶链式反应-微阵列技术检测了14例低分化甲状腺组织、13例低分化嗜酸细胞癌、72例高分化甲状腺癌和8例正常甲状腺组织中768个miRNAs的表达。MiRNA在低分化甲状腺癌和低分化嗜酸细胞癌中的表达不同，在聚类分析中显示出个别的聚集性。与正常甲状腺组织相比，两种肿瘤均表现为miR-125a-5p、-15a-3p、-182、-183-3p、-222、-222-5p表达上调，miR-130b、-139-5p、-150、-193a-5p、-219-5p、-23b、-451、-455-3p和miR-886-3p表达下调。此外，嗜酸性低分化甲状腺癌中miR-221和miR-885-5p表达上调。在低分化和高分化肿瘤中，miRNA的表达也存在差异。CHAID算法使用miR-23b和miR-150作为分离器，能够以73-79%的准确率区分低分化和高分化的甲状腺癌。Kaplan-Meier和多变量分析显示，在低分化和嗜酸性低分化甲状腺癌中，肿瘤复发(miR-23b)和肿瘤特异性死亡(miR-150)显著相关。与高分化甲状腺癌相比，miRNA在普通型和嗜酸性低分化甲状腺癌中的表达不同，可用于区分这些肿瘤类型。新发现的解除调控的miRNAs(miR-150，miR-23b)具有在临床环境中用于提供预后和诊断信息的潜力。
The diagnosis of conventional and oncocytic poorly differentiated thyroid carcinomas is difficult. The aim of this study was to characterize their largely unknown miRNA expression profile and to compare it to well differentiated thyroid tumors as well as to identify miRNAs which could potentially serve as diagnostic and prognostic markers. A total of 14 poorly differentiated, 13 oncocytic poorly differentiated, 72 well differentiated thyroid carcinomas and 8 normal thyroid specimens were studied for expression of 768 miRNAs using PCR-Microarrays. MiRNA expression was different between poorly differentiated and oncocytic poorly differentiated thyroid carcinomas demonstrating individual clusters on the clustering analysis. Both tumor types showed upregulation of miR-125a-5p, -15a-3p, -182, -183-3p, -222, -222-5p and downregulation of miR-130b, -139-5p, -150, -193a-5p, -219-5p, -23b, -451, -455-3p and of miR-886-3p as compared to normal thyroid tissue. In addition, the oncocytic poorly differentiated thyroid carcinomas demonstrated upregulation of miR-221 and miR-885-5p. The difference in expression was also observed between miRNA expression in poorly differentiated and well differentiated tumors. The CHAID algorithm allowed to separate poorly differentiated from well differentiated thyroid carcinomas with a 73–79% accuracy using miR-23b and miR-150 as a separator. Kaplan-Meier and multivariate analysis showed a significant association with tumor relapses (for miR-23b) and with tumor specific death (for miR-150) in poorly differentiated and oncocytic poorly differentiated thyroid carcinomas. MiRNA expression is different in conventional and oncocytic poorly differentiated thyroid carcinomas in comparison to well differentiated thyroid cancers and can be used for discrimination between these tumor types. The newly identified deregulated miRNAs (miR-150, miR-23b) bear the potential to be used in a clinical setting delivering prognostic and diagnostic information.