miRNA 表达谱阵列鉴定出传统和嗜酸细胞滤泡状甲状腺癌的新型诊断标志物。
MicroRNA expression array identifies novel diagnostic markers for conventional and oncocytic follicular thyroid carcinomas.
机构信息
Department of Pathology and Laboratory Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15213, USA.
出版信息
J Clin Endocrinol Metab. 2013 Jan;98(1):E1-7. doi: 10.1210/jc.2012-2694. Epub 2012 Nov 12.
OBJECTIVE
The most difficult thyroid tumors to be diagnosed by cytology and histology are conventional follicular carcinomas (cFTCs) and oncocytic follicular carcinomas (oFTCs). Several microRNAs (miRNAs) have been previously found to be consistently deregulated in papillary thyroid carcinomas; however, very limited information is available for cFTC and oFTC. The aim of this study was to explore miRNA deregulation and find candidate miRNA markers for follicular carcinomas that can be used diagnostically.
DESIGN
Thirty-eight follicular thyroid carcinomas (21 cFTCs, 17 oFTCs) and 10 normal thyroid tissue samples were studied for expression of 381 miRNAs using human microarray assays. Expression of deregulated miRNAs was confirmed by individual RT-PCR assays in all samples. In addition, 11 follicular adenomas, two hyperplastic nodules (HNs), and 19 fine-needle aspiration samples were studied for expression of novel miRNA markers detected in this study.
RESULTS
The unsupervised hierarchical clustering analysis demonstrated individual clusters for cFTC and oFTC, indicating the difference in miRNA expression between these tumor types. Both cFTCs and oFTCs showed an up-regulation of miR-182/-183/-221/-222/-125a-3p and a down-regulation of miR-542-5p/-574-3p/-455/-199a. Novel miRNA (miR-885-5p) was found to be strongly up-regulated (>40-fold) in oFTCs but not in cFTCs, follicular adenomas, and HNs. The classification and regression tree algorithm applied to fine-needle aspiration samples demonstrated that three dysregulated miRNAs (miR-885-5p/-221/-574-3p) allowed distinguishing follicular thyroid carcinomas from benign HNs with high accuracy.
CONCLUSIONS
In this study we demonstrate that different histopathological types of follicular thyroid carcinomas have distinct miRNA expression profiles. MiR-885-5p is highly up-regulated in oncocytic follicular carcinomas and may serve as a diagnostic marker for these tumors. A small set of deregulated miRNAs allows for an accurate discrimination between follicular carcinomas and hyperplastic nodules and can be used diagnostically in fine-needle aspiration biopsies.
目的
细胞学和组织学诊断最困难的甲状腺肿瘤是传统滤泡癌（cFTC）和嗜酸细胞滤泡癌（oFTC）。先前已经发现几种 microRNAs（miRNAs）在甲状腺乳头状癌中持续失调；然而，关于 cFTC 和 oFTC 的信息非常有限。本研究旨在探索 miRNA 失调，并找到可用于诊断滤泡癌的候选 miRNA 标志物。
设计
研究了 38 例滤泡性甲状腺癌（21 例 cFTC，17 例 oFTC）和 10 例正常甲状腺组织样本，使用人类微阵列检测 381 种 miRNA 的表达。通过个体 RT-PCR 检测在所有样本中证实了失调 miRNA 的表达。此外，研究了 11 例滤泡性腺瘤、2 例增生性结节（HN）和 19 例细针抽吸样本中本研究检测到的新型 miRNA 标志物的表达。
结果
无监督层次聚类分析显示 cFTC 和 oFTC 分别为单个聚类，表明这些肿瘤类型之间的 miRNA 表达存在差异。cFTC 和 oFTC 均表现出 miR-182/-183/-221/-222/-125a-3p 的上调和 miR-542-5p/-574-3p/-455/-199a 的下调。新型 miRNA（miR-885-5p）在 oFTC 中强烈上调（>40 倍），而在 cFTC、滤泡性腺瘤和 HN 中则没有。应用于细针抽吸样本的分类回归树算法表明，三个失调 miRNA（miR-885-5p/-221/-574-3p）可以高精度地区分滤泡性甲状腺癌与良性 HN。
结论
在这项研究中，我们证明了不同组织病理学类型的滤泡性甲状腺癌具有不同的 miRNA 表达谱。miR-885-5p 在嗜酸细胞滤泡癌中高度上调，可能作为这些肿瘤的诊断标志物。一小部分失调 miRNA 可准确区分滤泡癌和增生性结节，并可在细针抽吸活检中用于诊断。
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