评估不确定和RAS突变的甲状腺结节管理中更新的microRNA分类器的临床性能：一项多机构研究

将microRNA标记与下一代测序面板整合可以增强细胞学上不确定甲状腺结节的风险评估。 thygenext-Thyramirv1乘数测试版本1在风险分离的RAS突变不确定的甲状腺结节方面证明了有限的效用。我们试图在临床实践中验证更新的ThyramiRV2平台。使用先前研究的Bethesda III/IV Nodules的多机构同类群，对三层的MicroRNA分类器进行了thygenext/Thyramirv2，并具有阳性结果，其积极的结果具有恶性≥10％的风险。此外，评估了ThyramiRV2在RAS熔化的不确定甲状腺结节中的临床实用性。在366中，不确定的甲状腺结节，thyramirv2平台产生了30.3％的正售率。 ThyramiRV2平台+结节具有更高的手术率（63.9％vs 36.1％，p <.0001）和癌症/非侵入性卵泡甲状腺肿瘤，具有乳头状核特征诊断（65.9％vs 25.0％，P <.0001），而不是Thyramirv2 Plastman Plastman Nodules。与乘以ThyramiRV2平台的诊断测试参数相比，与MultipLatform测试版本1相比，并未显着改善。在68个RAS突变结节中，ThyramiRV2分别将36.8％，55.9％和7.4％归类为正，中度和阴性。所有中等结节的恶性肿瘤风险≥10％，并与阳性队列结合使用。手术率（81.0％vs 60.0％，p = .272）或癌/无创卵泡甲状腺肿瘤没有显着差异，具有乳头状的核特征诊断（47.6％vs 40.6％vs 40.0％，p> .999，p> .999）之间的阳性阳性/中度/中度负组和负组之间。对于RAS突变的结节，thyramiRV2表现出提高的敏感性（93.8％vs 64.7，P = .003）和降低的特异性（4.5％vs 34.8％，P = .008），与Thygenext-Thyramirv1相比，具有可比性的预测值1，且具有比较（58.8％vs 59.5％，p = .864）.ThyramiRV2平台与thygenext-thyramirv1倍增测试版本1相比，thyramirv2平台并不能改善不确定的甲状腺结节恶性分层。thyramirv2改善了恶性Ras-Mutated Nodule的检测，但增加了虚假毒性。有必要更好地表征该分类器的性能参数，以便更好地表征与手术病理学结果相关的更大的RAS组合的未来研究。

Integrating microRNA markers with next-generation sequencing panels may enhance risk assessment of cytologically indeterminate thyroid nodules. The ThyGeNEXT-ThyraMIRv1 multiplatform test version 1 demonstrated limited utility in risk-stratifying RAS-mutated indeterminate thyroid nodules. We sought to validate the updated ThyraMIRv2 platform in clinical practice.ThyGeNEXT/ThyraMIRv2, a 3-tiered microRNA classifier, were evaluated using a previously studied multi-institutional cohort of Bethesda III/IV nodules, with positive results having risk of malignancy ≥10%. In addition, ThyraMIRv2's clinical utility in RAS-mutated indeterminate thyroid nodules was assessed.In 366 indeterminate thyroid nodules, ThyraMIRv2 platform yielded a 30.3% positive-call rate. ThyraMIRv2 platform + nodules had greater operative rates (63.9% vs 36.1%, P < .0001) and cancer/noninvasive follicular thyroid neoplasm with papillary-like nuclear features diagnosis (65.9% vs 25.0%, P < .0001) than ThyraMIRv2 platform nodules. Compared with multiplatform test version 1, ThyraMIRv2 platform's diagnostic testing parameters did not improve significantly. Among 68 RAS-mutated nodules, ThyraMIRv2 classified 36.8%, 55.9%, and 7.4% as positive, moderate, and negative, respectively. All moderate nodules had risk of malignancy ≥10% and were combined with the positive cohort. No significant differences existed in operative rate (81.0% vs 60.0%, P = .272) or cancer/noninvasive follicular thyroid neoplasm with papillary-like nuclear features diagnosis (47.6% vs 40.0%, P > .999) between RAS-mutated positive/moderate and negative groups. For RAS-mutated nodules, ThyraMIRv2 demonstrated improved sensitivity (93.8% vs 64.7, P = .003) and decreased specificity (4.5% vs 34.8%, P = .008) compared with ThyGeNEXT-ThyraMIRv1 multiplatform test version 1, with comparable negative predictive value (33.3% vs 40.0%, P = .731) and positive predictive value (58.8% vs 59.5%, P = .864).ThyraMIRv2 platform does not improve indeterminate thyroid nodule malignancy stratification compared to ThyGeNEXT-ThyraMIRv1 multiplatform test version 1. ThyraMIRv2 improves malignant RAS-mutated nodule detection but increases false positives. Future studies encompassing a larger cohort of RAS-mutated with surgical pathology results are warranted to better characterize the performance parameters of this classifier.