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Abstract：
The repertoire of microRNAs (miRNAs) in thyroid carcinomas starts to be elucidated. Among differentiated thyroid carcinomas (DTCs), papillary thyroid carcinoma (PTC) is the most frequent. The assessment of miRNAs expression may contribute to refine the pre-surgical diagnosis in order to obtain a personalized and more effective treatment for patients.
This study aims to evaluate (1) the miRNAs in a series of DTCs, and their association with the presence of selected genetic mutations in order to improve diagnosis and predict the biologic behavior of DTC/PTC. (2) The reliability of molecular tests in Ultrasound-guided Fine Needle Aspiration Cytology (US-FNAC) for a more precise preoperative diagnosis.
This series includes 176 samples (98 cytology and 78 histology samples) obtained from 106 patients submitted to surgery, including 13 benign lesions (controls) and 93 DTCs (cases). The microRNA expression was assessed for miR-146b, miR-221, miR-222, and miR-15a through quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). The results were analyzed by the 2-ΔΔCT method, using miR16 as an endogenous control. Regarding PTC diagnosis, the discriminative ability of miRNAs expression was assessed by the area under the Receiver Operating Characteristic Curve (AUC). In PTCs, the association of miRNAs expression, clinicopathological features, and genetic mutations (BRAF, RAS, and TERTp) was evaluated.
All the analyzed miRNAs presented a tendency to be overexpressed in DTCs/PTCs when compared with benign lesions, both in cytology and histology samples. In cytology, miRNAs expression levels were higher in malignant tumors than in benign tumors. In histology, the discriminative abilities regarding PTC diagnosis were as follows: miR-146b (AUC 0.94, 95% CI 0.87-1), miR-221 (AUC 0.79, 95% CI 0.68-0.9), miR-222 (AUC 0.76, 95% CI 0.63-0.89), and miR-15a (AUC 0.85, 95% CI 0.74-0.97). miR-146b showed 89% sensitivity (se) and 87% specificity (sp); miR-221 se = 68.4, sp = 90; miR-222 se = 73, sp = 70; and mi-R15a se = 72, sp = 80. MicroRNAs were associated with worst-prognosis clinicopathological characteristics in PTCs (p < 0.05), particularly for miR-222. Our data reveal a significant association between higher expression levels of miR-146b, miR-221, and miR-222 in the presence of the BRAF mutation (p < 0.001) and miR-146b (p = 0.016) and miR-221 (p = 0.010) with the RAS mutation, suggesting an interplay of these mutations with miRNAs expression. Despite this study having a relatively small sample size, overexpression of miRNAs in cytology may contribute to a more precise preoperative diagnosis. The miRNAs presented a good discriminative ability in PTC diagnosis. The association between the miRNAs expression profile and genetic alterations can be advantageous for an accurate diagnosis of DTCs/PTCs in FNAC.
This study aims to evaluate (1) the miRNAs in a series of DTCs, and their association with the presence of selected genetic mutations in order to improve diagnosis and predict the biologic behavior of DTC/PTC. (2) The reliability of molecular tests in Ultrasound-guided Fine Needle Aspiration Cytology (US-FNAC) for a more precise preoperative diagnosis.
This series includes 176 samples (98 cytology and 78 histology samples) obtained from 106 patients submitted to surgery, including 13 benign lesions (controls) and 93 DTCs (cases). The microRNA expression was assessed for miR-146b, miR-221, miR-222, and miR-15a through quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). The results were analyzed by the 2-ΔΔCT method, using miR16 as an endogenous control. Regarding PTC diagnosis, the discriminative ability of miRNAs expression was assessed by the area under the Receiver Operating Characteristic Curve (AUC). In PTCs, the association of miRNAs expression, clinicopathological features, and genetic mutations (BRAF, RAS, and TERTp) was evaluated.
All the analyzed miRNAs presented a tendency to be overexpressed in DTCs/PTCs when compared with benign lesions, both in cytology and histology samples. In cytology, miRNAs expression levels were higher in malignant tumors than in benign tumors. In histology, the discriminative abilities regarding PTC diagnosis were as follows: miR-146b (AUC 0.94, 95% CI 0.87-1), miR-221 (AUC 0.79, 95% CI 0.68-0.9), miR-222 (AUC 0.76, 95% CI 0.63-0.89), and miR-15a (AUC 0.85, 95% CI 0.74-0.97). miR-146b showed 89% sensitivity (se) and 87% specificity (sp); miR-221 se = 68.4, sp = 90; miR-222 se = 73, sp = 70; and mi-R15a se = 72, sp = 80. MicroRNAs were associated with worst-prognosis clinicopathological characteristics in PTCs (p < 0.05), particularly for miR-222. Our data reveal a significant association between higher expression levels of miR-146b, miR-221, and miR-222 in the presence of the BRAF mutation (p < 0.001) and miR-146b (p = 0.016) and miR-221 (p = 0.010) with the RAS mutation, suggesting an interplay of these mutations with miRNAs expression. Despite this study having a relatively small sample size, overexpression of miRNAs in cytology may contribute to a more precise preoperative diagnosis. The miRNAs presented a good discriminative ability in PTC diagnosis. The association between the miRNAs expression profile and genetic alterations can be advantageous for an accurate diagnosis of DTCs/PTCs in FNAC.
摘要：
背景：甲状腺癌中的microRNA（miRNA）库开始被阐明。在分化型甲状腺癌（DTC）中，甲状腺乳头状癌（PTC）是最常见的。miRNA表达的评估可能有助于改善手术前诊断，以便为患者获得个性化和更有效的治疗。
目的：本研究旨在评估（1）一系列DTC中的miRNA，以及它们与所选择的基因突变的存在的关联，以提高诊断和预测DTC/PTC的生物学行为。(2)超声引导下细针穿刺细胞学(US-FNAC)中分子检测技术的可靠性,用于更精确的术前诊断。
方法：本系列包括从106例接受手术的患者中获得的176个样本（98个细胞学样本和78个组织学样本），包括13个良性病变（对照）和93个DTC（病例）。评估miR-146b的microRNA表达，miR-221，miR-222和miR-15a通过定量逆转录酶聚合酶链反应（qRT-PCR）。结果用2-ΔΔCT法分析，使用miR16作为内源性对照。关于PTC诊断，通过接受者工作特征曲线(AUC)下面积来评估miRNA表达的辨别能力。在PTC中,miRNA表达的关联，临床病理特征，和基因突变（BRAF，RAS,和TERTp）进行评估。
结论：与良性病变相比，所有分析的miRNA在DTC/PTC中呈现过表达的趋势，细胞学和组织学样本。在细胞学中，miRNA在恶性肿瘤中的表达水平高于良性肿瘤。在组织学上，关于PTC诊断的判别能力如下：miR-146b（AUC0.94，95％CI0.87-1），miR-221（AUC0.79，95%CI0.68-0.9），miR-222（AUC0.76，95%CI0.63-0.89），和miR-15a（AUC0.85，95%CI0.74-0.97）。miR-146b显示89%的灵敏度(se)和87%的特异性(sp);miR-221se=68.4,sp=90;miR-222se=73,sp=70;和mi-R15ase=72,sp=80。MicroRNAs与PTCs预后最差的临床病理特征相关(p<0.05),特别是对于miR-222。我们的数据揭示了miR-146b较高表达水平之间的显著关联，miR-221和miR-222在存在BRAF突变（p<0.001）和miR-146b（p=0.016）和miR-221（p=0.010）的情况下具有RAS突变，提示这些突变与miRNAs表达的相互作用。尽管这项研究的样本量相对较小，miRNA在细胞学中的过表达可能有助于更精确的术前诊断。miRNA在PTC诊断中表现出良好的辨别能力。miRNA表达谱和遗传改变之间的关联对于FNAC中DTC/PTC的准确诊断可以是有利的。
目的：本研究旨在评估（1）一系列DTC中的miRNA，以及它们与所选择的基因突变的存在的关联，以提高诊断和预测DTC/PTC的生物学行为。(2)超声引导下细针穿刺细胞学(US-FNAC)中分子检测技术的可靠性,用于更精确的术前诊断。
方法：本系列包括从106例接受手术的患者中获得的176个样本（98个细胞学样本和78个组织学样本），包括13个良性病变（对照）和93个DTC（病例）。评估miR-146b的microRNA表达，miR-221，miR-222和miR-15a通过定量逆转录酶聚合酶链反应（qRT-PCR）。结果用2-ΔΔCT法分析，使用miR16作为内源性对照。关于PTC诊断，通过接受者工作特征曲线(AUC)下面积来评估miRNA表达的辨别能力。在PTC中,miRNA表达的关联，临床病理特征，和基因突变（BRAF，RAS,和TERTp）进行评估。
结论：与良性病变相比，所有分析的miRNA在DTC/PTC中呈现过表达的趋势，细胞学和组织学样本。在细胞学中，miRNA在恶性肿瘤中的表达水平高于良性肿瘤。在组织学上，关于PTC诊断的判别能力如下：miR-146b（AUC0.94，95％CI0.87-1），miR-221（AUC0.79，95%CI0.68-0.9），miR-222（AUC0.76，95%CI0.63-0.89），和miR-15a（AUC0.85，95%CI0.74-0.97）。miR-146b显示89%的灵敏度(se)和87%的特异性(sp);miR-221se=68.4,sp=90;miR-222se=73,sp=70;和mi-R15ase=72,sp=80。MicroRNAs与PTCs预后最差的临床病理特征相关(p<0.05),特别是对于miR-222。我们的数据揭示了miR-146b较高表达水平之间的显著关联，miR-221和miR-222在存在BRAF突变（p<0.001）和miR-146b（p=0.016）和miR-221（p=0.010）的情况下具有RAS突变，提示这些突变与miRNAs表达的相互作用。尽管这项研究的样本量相对较小，miRNA在细胞学中的过表达可能有助于更精确的术前诊断。miRNA在PTC诊断中表现出良好的辨别能力。miRNA表达谱和遗传改变之间的关联对于FNAC中DTC/PTC的准确诊断可以是有利的。
