Department of Molecular Medicine and Anatomy, Nippon Medical School, Tokyo, Japan.
Int J Oncol. 2013 Jun;42(6):1858-68. doi: 10.3892/ijo.2013.1879. Epub 2013 Apr 2.
Minimally invasive follicular thyroid carcinoma (MI-FTC) is characterized by limited capsular and/or vascular invasion with good long-term outcomes. However, some cases of MI-FTC show a poor prognosis because of severe distant metastasis (i.e., metastatic MI-FTC). Nonetheless, no method has been established for predicting the prognosis of MI-FTC. This study was conducted to identify novel prognostic factors for metastatic MI-FTC by the use of microRNA (miRNA). Thirty-four patients with MI-FTC were categorized into two groups: the metastatic group, M(+) (n=12) and the non-metastatic group, M(-) (n=22). In the M(+) group, distant metastasis was recognized after the initial operation established the diagnosis of MI-FTC. In the M(-) group, no distant metastasis was recognized postoperatively for ≥ 10 years. Using laser microdissection followed by quantitative real-time PCR and PCR arrays, we performed a comprehensive expression profiling of 667 miRNAs in formalin-fixed, paraffin-embedded samples from the initial MI-FTC operation. Furthermore, we assessed the potential use of miRNAs as novel biomarkers for the metastatic potential of MI-FTC by logistic regression analysis. Comprehensive quantitative analysis of miRNA expression in MI-FTC samples revealed that the miR-221/222 cluster (i.e., miR-221, miR-222 and miR-222*), miR-10b and miR-92a were significantly upregulated in the M(+) group compared with the M(-) group. Interestingly, the expression levels of these miRNAs were also shown to be upregulated in widely invasive FTC (WI-FTC; n=13) that has distant metastasis and worse prognosis, indicating a close similarity in the miRNA expression between metastatic MI-FTC and WI-FTC. Logistic regression analysis revealed that miR-10b made a significant contribution to prognosis (OR 19.759, 95% CI 1.433-272.355, p=0.026). Our findings suggest that miR-10b is a potential prognostic factor for evaluating the metastatic potential of MI-FTC at an initial operation stage.
局限性微小浸润滤泡状甲状腺癌（MI-FTC）的特点是包膜和/或血管侵犯有限，但长期预后良好。然而，有些 MI-FTC 病例由于严重的远处转移（即转移性 MI-FTC）而预后较差。尽管如此，目前尚无预测 MI-FTC 预后的方法。本研究旨在通过 microRNA（miRNA）来确定转移性 MI-FTC 的新型预后因素。34 例 MI-FTC 患者分为两组：转移性组 M(+)（n=12）和非转移性组 M(-)（n=22）。在 M(+)组中，在初始手术确定 MI-FTC 诊断后发现远处转移。在 M(-)组中，术后≥10 年未发现远处转移。使用激光显微切割，随后进行定量实时 PCR 和 PCR 阵列，我们对初始 MI-FTC 手术中福尔马林固定、石蜡包埋样本中的 667 种 miRNA 进行了全面的表达谱分析。此外，我们通过逻辑回归分析评估了 miRNA 作为 MI-FTC 转移潜能的新型生物标志物的潜在用途。对 MI-FTC 样本中 miRNA 表达的综合定量分析表明，miR-221/222 簇（即 miR-221、miR-222 和 miR-222*）、miR-10b 和 miR-92a 在 M(+)组中明显高于 M(-)组。有趣的是，这些 miRNA 的表达水平也在具有远处转移和更差预后的广泛浸润滤泡状甲状腺癌（WI-FTC；n=13）中升高，表明转移性 MI-FTC 和 WI-FTC 之间在 miRNA 表达上非常相似。逻辑回归分析表明，miR-10b 对预后有显著贡献（OR 19.759，95%CI 1.433-272.355，p=0.026）。我们的研究结果表明，miR-10b 可能是在初始手术阶段评估 MI-FTC 转移潜能的潜在预后因素。
