Sondermann Adriana, Andreghetto Flavia Maziero, Moulatlet Ana Carolina Bernardini, da Silva Victor Elivane, de Castro Marilia Germanos, Nunes Fábio Daumas, Brandão Lenine Garcia, Severino Patricia
Albert Einstein Research and Education Institute, Hospital Israelita Albert Einstein, Av. Albert Einstein, 627, São Paulo, SP, 05652-000, Brazil.
Clin Exp Metastasis. 2015 Aug;32(6):521-30. doi: 10.1007/s10585-015-9724-3. Epub 2015 May 26.
Despite low mortality rates, nodal recurrence in papillary thyroid carcinoma occurs in up to 20 % of patients. Emerging evidences indicate that dysregulated microRNAs are implicated in the process of metastasis. In the present study, we investigated whether miR-9, miR-10b, miR-21 and miR-146b levels are predictive of papillary thyroid carcinoma recurrence. Using macro-dissection followed by quantitative real-time PCR, we measured miR-9, miR-10b, miR-21 and miR-146b expression levels in formalin-fixed, paraffin-embedded samples of 66 patients with papillary thyroid carcinoma categorized into two groups: the recurrent group (n = 19) and the non-recurrent group (n = 47). All patients underwent total thyroidectomy and were followed for at least 120 months after surgery to be considered recurrence-free. Univariate and multivariate analysis were performed using the Cox proportional hazard model in order to identify associations between multiple clinical variables and microRNA expression levels and papillary thyroid carcinoma recurrence. MiR-9 and miR-21 expression levels were found to be significant prognostic factors for recurrence in patients with papillary thyroid carcinoma (HR = 1.48; 95 % CI 1.24-1.77, p < 0.001; and HR = 1.52; 95 % CI 1.18-1.94, p = 0.001; respectively). Multivariate analysis involving the expression level of miR-9 and miR-21 and various clinical parameters identified the expression of these microRNAs as independent prognostic factors for papillary thyroid cancer patients. In conclusion, our results support the potential clinical value of miR-9 and miR-21 as prognostic biomarkers for recurrence in papillary thyroid carcinoma.
尽管死亡率较低，但甲状腺乳头状癌患者中淋巴结复发率高达20%。新出现的证据表明，失调的微小RNA与转移过程有关。在本研究中，我们调查了miR-9、miR-10b、miR-21和miR-146b水平是否可预测甲状腺乳头状癌复发。通过大体解剖后进行定量实时PCR，我们测量了66例甲状腺乳头状癌患者福尔马林固定、石蜡包埋样本中miR-9、miR-10b、miR-21和miR-146b的表达水平，这些患者分为两组：复发组（n = 19）和未复发组（n = 47）。所有患者均接受了全甲状腺切除术，并在术后至少随访120个月以确定无复发。使用Cox比例风险模型进行单因素和多因素分析，以确定多个临床变量与微小RNA表达水平及甲状腺乳头状癌复发之间的关联。发现miR-9和miR-21表达水平是甲状腺乳头状癌患者复发的重要预后因素（HR = 1.48；95%CI 1.24 - 1.77，p < 0.001；以及HR = 1.52；95%CI 1.18 - 1.94，p = 0.001）。涉及miR-9和miR-21表达水平及各种临床参数的多因素分析确定这些微小RNA的表达是甲状腺乳头状癌患者的独立预后因素。总之，我们的结果支持miR-9和miR-21作为甲状腺乳头状癌复发预后生物标志物的潜在临床价值。
