下调的 miR-7-5p 和 miR-548ar-5p 预测 BRAF 和 RAS 突变阴性的不明确甲状腺结节的恶性程度。
Down-regulation of miR-7-5p and miR-548ar-5p predicts malignancy in indeterminate thyroid nodules negative for BRAF and RAS mutations.
机构信息
University of Pisa, Department of Surgical, Medical, Molecular Pathology and Critical Area - via Savi, 10 56126, Pisa, Italy.
University of Pisa, Department of Clinical and Experimental Medicine - via Roma, 67 56126, Pisa, Italy.
出版信息
Endocrine. 2022 Jun;76(3):677-686. doi: 10.1007/s12020-022-03034-7. Epub 2022 Mar 26.
PURPOSE
The value of molecular markers in refining preoperative risk assessment of indeterminate thyroid nodules is being widely investigated. MicroRNAs (miRNA) are emerging as promising biomarkers for diagnostic and prognostic purposes. The aim of this study is to identify miRNAs specifically deregulated in mutation-negative indeterminate thyroid nodules.
METHODS
Ninety-eight nodules preoperatively diagnosed as TIR 3A or TIR 3B with available histological diagnosis of follicular adenoma (FA), noninvasive follicular neoplasm with papillary-like nuclear features (NIFTP), and follicular variant papillary thyroid carcinoma (FV-PTC) have been retrospectively selected. Mutations in BRAF and RAS genes have been tested in all samples by real-time PCR; miRNAs were purified from cytology slides of 60 samples; expression analysis of 798 miRNAs was measured by the nCounter system.
RESULTS
Point mutations in BRAF and RAS genes were detected in 32 out of 98 nodules (32.7%), the majority of which in FV-PTCs. Differential expression of miRNA in wild-type nodules highlighted that two miRNAs, namely miR-7-5p and miR-548ar-5p, were downregulated in FV-PTCs compared to FAs. The combined expression of these miRNAs, tested by ROC analysis, showed an area under the curve of 0.79. Sensitivity and negative predictive value were high both in wild-type (93% and 92%, respectively) and in mutated nodules (94% and 85%, respectively).
CONCLUSION
The analysis of miR-7-5p and miR-548ar-5p expression in indeterminate thyroid nodules demonstrated a promising value in ruling out malignancy.
目的
分子标志物在细化术前不确定甲状腺结节风险评估中的价值正受到广泛研究。microRNAs（miRNA）作为诊断和预后目的有前途的生物标志物正在出现。本研究旨在确定突变阴性不确定甲状腺结节中特异性下调的 miRNA。
方法
回顾性选择 98 个术前诊断为 TIR 3A 或 TIR 3B 的结节，其组织学诊断为滤泡性腺瘤（FA）、具有乳头状核特征的非侵袭性滤泡性肿瘤（NIFTP）和滤泡状变异型甲状腺癌（FV-PTC）。通过实时 PCR 测试所有样本中的 BRAF 和 RAS 基因突变；从 60 个样本的细胞学载玻片纯化 miRNA；通过 nCounter 系统测量 798 个 miRNA 的表达分析。
结果
在 98 个结节中的 32 个（32.7%）中检测到 BRAF 和 RAS 基因的点突变，其中大多数为 FV-PTC。野生型结节中 miRNA 的差异表达突出表明，与 FA 相比，两种 miRNA，即 miR-7-5p 和 miR-548ar-5p，在 FV-PTC 中下调。通过 ROC 分析测试这些 miRNA 的联合表达，曲线下面积为 0.79。在野生型（分别为 93%和 92%）和突变型结节（分别为 94%和 85%）中，敏感性和阴性预测值均较高。
结论
在不确定的甲状腺结节中分析 miR-7-5p 和 miR-548ar-5p 的表达显示出排除恶性肿瘤的有前途的价值。
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