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

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。细针穿刺细胞学（FNAC）是一种非常敏感和特异性的甲状腺结节鉴别诊断工具。然而，它显示不确定的结果是滤泡增生（滤泡性甲状腺癌和滤泡性腺瘤的特征）高达20%。此外，冷性甲状腺结节（ctn）的分子病因学仍然有限，ctn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，特定的CTN mRNA增殖特征仅部分与甲状腺乳头状癌的增殖特征重叠。此外，对不同肿瘤类型的研究表明，microrna （miRNAs）对增殖有显著的调节作用。此外，最近有研究表明，在无法根据肿瘤组织学确定的肿瘤类型的鉴别诊断中，miRNA谱优于mRNA谱。因此，本提案的第一个目标是确定并验证滤泡性甲状腺癌和冷甲状腺结节（主要是滤泡性腺瘤）mRNA增殖特征的miRNA相关，这可能解释增殖增加（FTCs和ctn中常见的miRNA集），并最有可能驱动恶性转化（FTCs的私有miRNA集）。第二个目标将是研究ctn和FTCs的私有miRNA特征，以用于诊断FNAC结果不确定的滤泡增生。

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.