MicroRNA signature of thyroid tumors and its possible diagnostic application for the differential diagnosis of follicular thyroid cancer and follicular adenomas

甲状腺肿瘤的 MicroRNA 特征及其在滤泡性甲状腺癌和滤泡性腺瘤鉴别诊断中的可能诊断应用

• 批准号: 115998009
• 负责人: Dr. Markus Eszlinger
• 金额: --
• 依托单位: Comprehensive Cancer Centre
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2009
• 资助国家: 德国
• 起止时间: 2008-12-31 至 2010-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/115998009?language=en
• 关键词: MicroRNA; signature; thyroid; tumors; its

The differentiation of the rarely occurring thyroid carcinoma from the frequently occurring benign thyroid nodules is a frequent and challenging issue. Fine-needle aspiration cytology (FNAC) is a very sensitive and specific tool for the differential diagnosis of thyroid nodules. However, it reveals the inconclusive result of follicular proliferation (characteristic for both follicular thyroid carcinoma and follicular adenoma) in up to 20%. Furthermore, the molecular etiology of cold thyroid nodules (CTNs) which comprise approximately 85% of thyroid nodules and which are characterized by increased proliferation, is still limited. However, recent microarray studies showed a specific CTN mRNA proliferation signature that overlaps only partly with the proliferation signature found in papillary thyroid carcinoma. Moreover, investigations of different tumor types revealed a prominent modulation of proliferation by microRNAs (miRNAs). Furthermore, it has recently been shown that miRNA profiles are superior to mRNA profiles in the differential diagnosis of tumor types that cannot be determined on the basis of tumor histologies. Therefore, the first goal of this proposal is to identify and to verify the miRNA correlates of the mRNA proliferation signatures of follicular thyroid carcinomas and cold thyroid nodules (mostly follicular adenomas), which are likely to explain the increased proliferation (common miRNA set in FTCs and CTNs) and which most likely drive malignant transformation (private miRNA set of FTCs). The second goal will be to investigate the private miRNA signatures of CTNs and FTCs for their diagnostic application for the inconclusive FNAC result follicular proliferation.

罕见的甲状腺癌与多发的良性甲状腺结节的鉴别是一个常见且具有挑战性的问题。细针吸取细胞学(FNAC)是鉴别诊断甲状腺结节的一种非常敏感和特异的工具。然而，它揭示了高达20%的滤泡增殖(滤泡性甲状腺癌和滤泡腺瘤的特征)的不确定结果。此外，冷性甲状腺结节(CTN)的分子病因学仍然有限，它约占甲状腺结节的85%，其特征是增殖增加。然而，最近的微阵列研究显示了一个特定的CTN mRNA增殖特征，该特征仅与乳头状甲状腺癌中发现的增殖特征部分重叠。此外，对不同类型肿瘤的研究表明，microRNAs(MiRNAs)对细胞增殖有显著的调节作用。此外，最近的研究表明，在不能根据肿瘤组织学确定的肿瘤类型的鉴别诊断中，miRNA图谱优于mRNA图谱。因此，这项建议的第一个目标是识别和验证滤泡性甲状腺癌和冷结节(主要是滤泡性腺瘤)的miRNA增殖特征之间的相关性，这可能解释了甲状腺滤泡性癌和甲状腺滤泡性结节(FTC和CTN中常见的miRNA集)的增殖增加，以及最有可能推动恶性转化的miRNA集(FTCs的私有miRNA集)。第二个目标将是研究CTN和FTCs的私有miRNA签名，以用于诊断FNAC结果不确定的卵泡增殖。