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miR-221 的过表达与甲状腺乳头状癌侵袭性临床病理特征和 BRAF 突变相关。

Overexpression of miR-221 is associated with aggressive clinicopathologic characteristics and the BRAF mutation in papillary thyroid carcinomas.

机构信息

Department of Oncology, The First Affiliated Hospital of Wenzhou Medical College, No. 2 Fuxue Lane, Wenzhou, Zhejiang, China.

出版信息

Med Oncol. 2012 Dec;29(5):3360-6. doi: 10.1007/s12032-012-0315-8. Epub 2012 Aug 2.

DOI:10.1007/s12032-012-0315-8
PMID:22855362
Abstract

Correlation between clinicopathogenetic features and the expression of specific miRNAs is unclear in papillary thyroid carcinoma (PTC). We therefore sought to assess whether miR-221 was associated with aggressive clinicopathologic characteristics and the BRAF mutation. We studied the expression levels of miR-221 using northern blot quantitated by scion image in 51 cases of PTCs. The status of BRAF of PTCs was analyzed through direct DNA sequencing. Mann-Whitney U test was used to analyze different expression of miR-221 in PTCs with distinct clinicopathogenetic characteristics including gender, age, tumor size, multifocality, extrathyroidal invasion, disease stages, node metastasis, and BRAF status. Compared with the normal thyroid tissues, the relative expression of miR-221 in tumor tissues was significantly upregulated (p < 0.001). Overexpression of miR-221 was significantly associated with extrathyroidal invasion (p = 0.001), lymph node metastasis (p = 0.046), advanced disease stages III-IV (p = 0.001), and the BRAF mutation (p = 0.014). While among BRAF wild tumors, miR-221 was only associated with extarthyroidal invasion, it showed strong association with all above aggressive features among BRAF mutation tumors. MiR-221 may be of potential importance in determining the aggressive properties of PTCs including the BRAF mutation, and it may further refine the risk stratification by BRAF mutation in PTCs.

摘要

在甲状腺乳头状癌(PTC)中,临床病理特征与特定 miRNA 的表达之间的相关性尚不清楚。因此,我们试图评估 miR-221 是否与侵袭性临床病理特征和 BRAF 突变有关。我们使用Northern blot 检测了 51 例 PTC 中 miR-221 的表达水平,并通过 Scion Image 进行定量分析。通过直接 DNA 测序分析 PTCs 的 BRAF 状态。Mann-Whitney U 检验用于分析具有不同临床病理特征(包括性别、年龄、肿瘤大小、多灶性、甲状腺外侵犯、疾病分期、淋巴结转移和 BRAF 状态)的 PTC 中 miR-221 的不同表达。与正常甲状腺组织相比,肿瘤组织中 miR-221 的相对表达明显上调(p < 0.001)。miR-221 的过表达与甲状腺外侵犯(p = 0.001)、淋巴结转移(p = 0.046)、晚期疾病分期 III-IV(p = 0.001)和 BRAF 突变(p = 0.014)显著相关。而在 BRAF 野生型肿瘤中,miR-221 仅与甲状腺外侵犯有关,但在 BRAF 突变型肿瘤中与所有上述侵袭性特征均有强烈关联。miR-221 可能对确定 PTC 的侵袭性特征(包括 BRAF 突变)具有重要意义,并且可能通过 BRAF 突变进一步细化 PTC 的风险分层。

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