目的：1. 评价新型多基因检测平台在甲状腺细胞学诊断不明确结节中的诊断价

值，通过分子检测来解决诊断不明确结节分流管理中的难题。2.探讨新型多基因检

测平台在甲状腺癌高恶性风险地区的应用模式。

方法：收集中国医学科学院肿瘤医院自 2018 年 12 月到 2019 年 10 月收治的 2392

例进行甲状腺细针穿刺并有细胞学诊断结果的患者信息。细胞学诊断不明确病例

共 263 例，排除不符合纳入标准及 DNA 或 RNA 量不足的病例后，剩余 140 例。

对这 140 例细胞学诊断不明确病例进行新型多基因分子检测。该检测平台可检测

基因点突变、插入/缺失、融合及基因的表达情况，并给出两种检测类型的结果即

RNA 分类器检测结果和 DNA-RNA 分类器检测结果。最后将分子检测结果同组织

病理结果进行比较，分析新型多基因检测在细胞学诊断不明确甲状腺结节中的诊

断效能。

结果：总共有 140 例细胞学诊断不明确病例完成了分子检测，其中 58 例有术后病

理结果，15 例为良性；10 例为交界性肿瘤；33 例为恶性，这组病例的恶性（包括

交界性病变）风险为 74.1%。RNA 分类器的敏感性、特异性、阳性预测值、阴性

预测值及受试者工作特征曲线（receiver operating characteristic, ROC）的曲线下面

积（Area under curve，AUC）分别是 93.0%、40.0%、81.6%、66.7%和 0.81 。

DNA-RNA 分类器的敏感性、特异性、阳性预测值、阴性预测值及受试者工作特征

曲线（receiver operating characteristic, ROC）的曲线下面积（Area under curve，

AUC）分别是 88.4%、53.3%、84.4%、61.5%和 0.77 。在 DNA-RNA 分类器中，

检出 26 个基因突变和融合，包括 5 个 BRAF v600E 突变，2 个 BRAF K601E 突

变，10 个 RAS 突变，2 个 TERT 突变，7 个基因融合（1 个 CCDC6-RET ，1 个

NCOA4-RET ，4 个 ETV6-NTRK3 ，1 个 STRN-ALK）。

结论：新型分子检测平台在细胞学诊断不明确结节再分类中有一定的诊断意义。

基于本研究中诊断不明确结节的高恶性风险值，在本研究所的临床实践中我们建

议将 RNA 和 DNA-RNA 检测作为“rule in”检测。分子检测平台是作为“rule in”或者

“rule out”的应用模式与诊断不明确结节的恶性风险密切相关。

关键词：DNA-RNA 检测；RNA 检测；细胞学诊断不明确结节；确诊检测；排除

检测。

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Objective: 1. To evaluate the diagnostic value of a novel molecular testing in stratifying

indeterminate thyroid nodules and explore the utility of molecular testing in the

management of indeterminate thyroid nodules. 2. To explore the application mode of

molecular testing in an area with high risk of malignancy in indeterminate thyroid

nodules.

Methods: 2392 patients performed thyroid fine needle aspiration in Cancer Hospital of

Chinese Academy of Medical Sciences from December 2018 to October 2019 were

enrolled. There was a total of 263 cases with indeterminate cytology, and after excluding

cases that did not meet the inclusion criteria and the amount of DNA or RNA was

insufficient, there were 140 remaining cases. The 140 cases with indeterminate cytology

were subjected to a novel molecular detection. The detection platform can detect gene

point mutation, insertion/deletion, fusion and gene expression, and provides two types of

detection results, namely RNA classifier detection results and DNA-RNA classifier

detection results. Finally, the molecular detection results were compared with the

histopathological results to analyze the diagnostic performance of the novel polygenic

detection in stratifying thyroid indeterminate nodules.

Results:

A total of 140 cases with indeterminate cytology completed molecular testing, of which

58 had postoperative pathological findings. Among 58 thyroid nodules with

indeterminate cytology, 15 were benign, 10 were borderline tumors, and 33 were

malignant. The overall risk of malignancy or borderline lesions was 74.1% in this cohort.

The sensitivity, specificity, positive predictive value, negative predictive value, and

receiver operating characteristic (ROC) area under the curve (AUC) of the RNA

classifier were 93.0%, 40.0%, 81.6%, 66.7% and 0.81, respectively. The sensitivity,

specificity, positive predictive value, negative predictive value, and receiver operating

characteristic (ROC) area under the curve (AUC) of the DNA-RNA classifier were

88.4%, 53.3%, 84.4%, 61.5% and 0.77, respectively. In the DNA-RNA classifier, 26

gene mutations and fusions were detected, including 5 BRAF v600E mutations, 2 BRAF

K601E mutations, 10 RAS mutations, 2 TERT mutations, and 7 gene fusions (1 CCDC6-

RET, 1 NCOA4-RET, 4 ETV6-NTRK3, 1 STRN-ALK).

Conclusion: The new molecular detection platform may play a role in the stratifying

thyroid nodules with indeterminate cytology diagnosis. Based on the high malignancy

risk value in indeterminate thyroid nodules achieved in this study, we recommend RNA 北京协和医学院中国医学科学院硕士学位论文 英文摘要

6

and DNA-RNA testing may be performed as "rule in" test in our clinical practice. The

application mode of molecular detection platform as "rule in" or "rule out" is determined

by the malignancy risk of undetermined nodules.

Key words: DNA-RNA testing; RNA testing; cytologically indeterminate thyroid

nodules; rule in test; rule out test.