1 Department of Pathology, Faculty of Medicine, Kuwait University , Safat, Kuwait .
2 Department of Pathology, Farwaniya Hospital , Kuwait City, Kuwait .
Thyroid. 2018 Mar;28(3):319-327. doi: 10.1089/thy.2017.0127. Epub 2018 Mar 2.
Papillary thyroid carcinoma (PTC) variants have several overlapping clinical and pathological features. The World Health Organization recently published a new classification of thyroid tumors containing significant revisions. Encapsulated papillary thyroid carcinoma (EPTC) has been recognized as a distinctive variant of PTC. The noninvasive encapsulated follicular variant of PTC has been reclassified as noninvasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTP). Different neoplasms are associated with different outcomes and require different clinical management. The objective of this study was to explore the miRNA expression patterns specific for classic PTC (cPTC), EPTC, follicular variant of PTC, and NIFTP in order to identify biomarkers of diagnostic and prognostic utility aiming for better clinical decisions.
The expression of 84 miRNAs was determined by quantitative real-time polymerase chain reaction in 113 thyroid tissues of PTC (classic, encapsulated, and follicular), NIFTP, and hyperplasia lesions. Expression of the same miRNAs was tested in pre- and postoperative whole-blood samples.
Several miRNAs were differentially expressed in the different groups. Expression profile of miRNAs in the tissue was similarly reflected in the circulation. Receiver operating characteristic curve analysis showed that miR-7-5p, miR-222-3p, and miR-146b-5p can discriminate between the different groups with high sensitivity and specificity. Downregulation of miR-144-3p, miR-15a-5p, miR-20a-5p, miR-32-5p miR-142-5p, miR-143-3p, and miR-20b-5p is associated with aggressive behavior in cPTC. Circulating miR-146b-5p, miR-222-3p, miR-155-5p, and miR-378a-3p are potential diagnostic and follow up biomarkers for PTC.
Downregulation of miR-7-5p discriminates NIFTP from hyperplasia. Upregulation of miR-222-3p discriminates follicular variant of PTC from NIFTP. High levels of miR-146b-5p distinctively characterize cPTC. These miRNAs are useful biomarkers in the diagnosis of PTC and NIFTP, and help to avoid unnecessary thyroidectomy and improve clinical management.
甲状腺乳头状癌（PTC）的变体具有几种重叠的临床和病理特征。世界卫生组织最近发布了一份包含重大修订的甲状腺肿瘤新分类。包膜型甲状腺乳头状癌（EPTC）已被认为是 PTC 的一种独特变体。非侵袭性包膜滤泡型 PTC 已被重新分类为具有乳头状核特征的非侵袭性滤泡性甲状腺肿瘤（NIFTP）。不同的肿瘤与不同的结果相关，并需要不同的临床管理。本研究的目的是探索经典 PTC（cPTC）、EPTC、滤泡变体 PTC 和 NIFTP 特有的 miRNA 表达模式，以确定具有诊断和预后效用的生物标志物，旨在做出更好的临床决策。
通过定量实时聚合酶链反应（qRT-PCR）在 113 例甲状腺 PTC（经典、包膜和滤泡）、NIFTP 和增生病变的组织中测定 84 种 miRNA 的表达。在术前和术后全血样本中测试了相同 miRNA 的表达。
不同组之间有几个 miRNA 表达差异。组织中的 miRNA 表达谱在循环中得到了相似的反映。受试者工作特征曲线分析显示，miR-7-5p、miR-222-3p 和 miR-146b-5p 可以高灵敏度和特异性地区分不同的组。miR-144-3p、miR-15a-5p、miR-20a-5p、miR-32-5p、miR-142-5p、miR-143-3p 和 miR-20b-5p 的下调与 cPTC 的侵袭性行为相关。循环 miR-146b-5p、miR-222-3p、miR-155-5p 和 miR-378a-3p 是 PTC 的潜在诊断和随访生物标志物。
miR-7-5p 的下调可将 NIFTP 与增生区分开来。miR-222-3p 的上调可将滤泡变体 PTC 与 NIFTP 区分开来。miR-146b-5p 的高水平可显著表征 cPTC。这些 miRNA 可用于 PTC 和 NIFTP 的诊断，并有助于避免不必要的甲状腺切除术并改善临床管理。
