Analysis of Deregulated miRNAs is Helpful to Distinguish Poorly Differentiated Thyroid Carcinoma from Papillary Thyroid Carcinoma
Analysis of Deregulated miRNAs is Helpful to Distinguish Poorly Differentiated Thyroid Carcinoma from Papillary Thyroid Carcinoma
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DOI：
10.1055/s-0029-1215593
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发表时间：
2009-06-01
影响因子：
2.2
通讯作者：
Schmid, K. W.
中科院分区：
文献类型：
--
作者：
Schwertheim, S.;Sheu, S-Y.;Schmid, K. W.
低分化甲状腺癌（PDTC）被定义为一种源自滤泡细胞的恶性肿瘤，在形态学和生物学上介于高分化甲状腺癌和未分化甲状腺癌（ATC）之间。在本研究中，我们检测了两组不同的微小RNA（miRNA）在15例PDTC（包括3例混合性PDTC/乳头状甲状腺癌[PTC]）、9例“纯”PTC和9例ATC中的表达水平。第一组（“组1”）：miRNA - 146b、- 181b、- 21、- 221、- 222，所有这些在乳头状甲状腺癌中均显著上调；第二组（“组2”）：miRNA - 30d、- 125b、- 26a、- 30a - 5p和let - 7c，所有这些在未分化甲状腺癌中均下调。与正常甲状腺组织相比，所有“组1”的miRNA在PTC中均显著上调（p < 0.001）；在ATC中，4/5的miRNA上调（p < 0.001），而在PDTC中，所有5种miRNA的表达水平与正常甲状腺组织无显著差异。“组2”的所有miRNA在PTC中均显著上调（p < 0.004），在ATC中下调（p < 0.03）；在PDTC中，只有3/5下调（p < 0.011）。所检测的所有10种miRNA在PTC和PDTC之间均有显著差异（p < 0.003）。然而，在混合性PDTC/PTC病例的组织学分化的PTC成分中，所检测的所有10种miRNA的表达水平与PDTC成分中的表达水平无显著差异，而6/10的miRNA与“纯”PTC有显著差异。我们的结果表明，对不同组的miRNA进行分析是区分PDTC和“纯”PTC的有用工具。此外，我们的研究结果表明，某些miRNA缺乏失调可能会筛选出一部分易于进展为PDTC的PTC。
Poorly differentiated thyroid carcinoma (PDTC) is defined as a malignant follicular cell derived neoplasm, both morphologically and biologically intermediate between well differentiated and anaplastic thyroid carcinoma (ATC). In the present study we investigated the expression levels of two distinct sets of miRNAs ('set 1': miRNA-146b, -181b, -21, -221, -222, all shown to be significantly upregulated in papillary thyroid carcinoma [PTC]; 'set 2': miRNA-3 0d, -125b, -26a, -30a-5p, and let7c, all downregulated in ATC) in a series of 15 PDTC (including 3 mixed PDTC/PTC), 9 'pure' PTC, and 9 ATC. Compared to normal thyroid tissue all 'set 1' miRNAs were significantly upregulated in PTC (p < 0.001); in ATC 4/5 miRNAs were upregulated (p < 0.001) whereas in PDTC the expression levels of all 5 miRNAs did not differ significantly from normal thyroid. All miRNAs of 'set 2' were significantly upregulated in PTC (p < 0.004) and downregulated in ATC (p < 0.03); in PDTC only 3/5 were downregulated (p < 0.011). All 10 miRNAs investigated differed significantly (p < 0.003) between PTC and PDTC. In the histologically differentiated PTC compound of mixed PDTC/PTC cases, however, miRNA expression levels of all 10 miRNAs investigated lacked significant difference from those found in the PDTC compound, whereas 6/10 miRNAs differed significantly from 'pure' PTC. Our results indicate that analysis of distinct sets of miRNAs represent useful tools to distinguish PDTC from 'pure' PTC. Additionally our findings suggest that lack of deregulation of some miRNAs may select a subset of PTC prone to progression to PDTC.