Institute of Biotechnology, Life Sciences Center, Vilnius University, LT- 10257, Sauletekio av. 7, Vilnius, Lithuania.
Institute of Endocrinology, Medical Academy, Lithuanian University of Health Sciences, LT-50161 Eiveniu str. 2, Kaunas, Lithuania.
Biomolecules. 2020 Apr 17;10(4):625. doi: 10.3390/biom10040625.
Many miRNAs and cancer-related mutations have been proposed as promising molecular markers of papillary thyroid carcinoma (PTC). However, there are limited data on the correlation between miRNA expression, BRAF mutation, and PTC recurrence. Therefore, to evaluate the potential of BRAF mutation and five selected miRNAs (-146b, -222, -21, -221, -181b) in predicting PTC recurrence, these molecular markers were analyzed in 400 formalin-fixed, paraffin-embedded PTC tissue specimens. The expression levels of miRNAs were measured using qRT-PCR. It was demonstrated that expression levels of all analyzed miRNAs are significantly higher in recurrent PTC than in non-recurrent PTC ( < 0.05). Moreover, higher expression levels of miR-146b, miR-222, miR-21, and miR-221 were associated with other clinicopathologic features of PTC, such as tumor size and lymph node metastases at initial surgery ( < 0.05). No significant differences in the frequency of BRAF mutation in recurrent PTC and non-recurrent PTC were determined. Our results suggest that miRNA expression profile differs in PTC that is prone to recurrence when compared to PTC that does not reoccur after the initial surgery while BRAF mutation frequency does not reflect the PTC recurrence status. However, the prognostic value of the analyzed miRNAs is rather limited in individual cases as the pattern of miRNA expression is highly overlapping between recurrent and non-recurrent PTC.
许多 miRNA 和与癌症相关的突变已被提议作为甲状腺乳头状癌 (PTC) 的有前途的分子标志物。然而,关于 miRNA 表达、BRAF 突变与 PTC 复发之间的相关性的数据有限。因此,为了评估 BRAF 突变和 5 种选定的 miRNA(-146b、-222、-21、-221、-181b)在预测 PTC 复发中的潜力,对 400 例福尔马林固定、石蜡包埋的 PTC 组织标本进行了这些分子标志物的分析。使用 qRT-PCR 测量 miRNA 的表达水平。结果表明,在复发的 PTC 中,所有分析的 miRNA 的表达水平均明显高于非复发的 PTC(<0.05)。此外,miR-146b、miR-222、miR-21 和 miR-221 的高表达水平与 PTC 的其他临床病理特征相关,例如初始手术时的肿瘤大小和淋巴结转移(<0.05)。在复发的 PTC 和非复发的 PTC 中,BRAF 突变的频率没有显著差异。我们的结果表明,与初始手术后不再复发的 PTC 相比,易复发的 PTC 中的 miRNA 表达谱不同,而 BRAF 突变频率并不能反映 PTC 的复发状态。然而,在个别病例中,分析的 miRNA 的预后价值相当有限,因为复发和非复发 PTC 之间的 miRNA 表达模式高度重叠。