Abstract: Background　Thyroid nodules are a common clinical problem.Although thyroid nodules fine needle aspiration cytology （FNAC） is the gold standard for identifying benign and malignant thyroid nodules，about 15%-30% of thyroid nodules cannot be identified by it.Therefore，there is an urgent need to find molecular markers that can effectively help identify thyroid nodules.Objective　To investigate the expression levels of microRNA-221 and microRNA-222 in thyroid FNAC specimens of patients with benign and malignant thyroid nodules and their diagnostic value for benign and malignant thyroid nodules.Methods　Sixty patients with thyroid nodules who met the research criteria in the First Affiliated Hospital of Kangda College of Nanjing Medical University from March 2015 to December 2017 were selected.All patients were examined by FNAC.The first diagnosis was malignant lesions in 17 cases，benign lesions in 34 cases，suspected malignant and undiagnosed lesions in 5 cases，follicular lesions in 2 cases and follicular tumors in 2 cases.The expression levels of miR-221 and miR-222 in thyroid nodules FNAC specimen of patients with benign and malignant lesions were compared.Take the results of pathological examination after operation as the gold standard，the working characteristic curve （ROC curve） of patients with malignant thyroid nodules diagnosed by miR-221 and miR-222 in thyroid nodules FNAC cytology was drawn，and the area under the ROC curve （AUC），sensitivity and specificity were calculated.The coincidence rates of thyroid nodules FNAC examination results and miR-221 and miR-222 in thyroid nodules FNAC examination specimens for the diagnosis of thyroid nodules were calculated.The expression levels of miR-221 and miR-222 in thyroid nodules FNAC samples of patients with different general data were compared.Results　Pathological examination showed 51 benign nodules and 9 malignant nodules in 60 patients after thyroidectomy.The expression levels of miR-221 and miR-222 in patients with malignant nodules were higher than those in patients with benign nodules （P<0.05）.The AUC of miR-221 in thyroid FNAC specimens for diagnosis of malignant thyroid nodules was 0.774 （0.691， 0.858）. The cut-off value was 2.77， the sensitivity was 80%， the specificity was 60.0%， and the Yoden index was 0.400. The AUC of miR-222 in thyroid FNAC specimens for diagnosis of malignant thyroid nodules was 0.759 （0.672， 0.845）. The cut-off value value was 2.73， the sensitivity was 76.7%， the specificity was 66.7%， and the Yoden index was 0.443. The coincidence rate of thyroid nodules FNAC examination results and thyroid nodules FNAC examination samples in the diagnosis of thyroid nodules by miR-221 and miR-222 was 80.0%.There was no significant difference in the expression levels of miR-221 and miR-222 between patients with different gender，age，maximum diameter of tumors，number of lesions，invasion of capsule，lymph node metastasis and TNM stage （P>0.05）.Conclusion　The expression levels of miR-221 and miR-222 in thyroid nodules FNAC specimen of patients with malignant thyroid gland were significantly increased.The diagnostic value of thyroid nodules FNAC alone in differentiating benign and malignant thyroid nodules was not high，but combined with thyroid nodules FNAC results，it could improve the diagnostic efficiency of benign and malignant thyroid nodules.

Key words: Thyroid nodule；MicroRNAs；miR-221；miR-222；Fine needle aspiration cytology；Diagnosis, differential

摘要： 背景　甲状腺结节是一种常见的临床问题，甲状腺细针穿刺吸取细胞学（FNAC）检查是临床常用的诊断良恶性甲状腺结节的检查方法，但15%~30%的患者无法确切诊断。因此，临床上迫切需要能有效帮助鉴别诊断良恶性甲状腺结节的生物学标志物。目的　探讨良恶性甲状腺结节患者甲状腺FNAC检查标本中miR-221、miR-222的表达水平及其对良恶性甲状腺结节的诊断价值。方法　选取2015年3月—2017年12月就诊于南京医科大学康达学院第一附属医院符合研究标准的甲状腺结节患者60例。患者均经甲状腺FNAC检查，初次诊断为恶性病变17例，良性病变34例，可疑恶性、未诊断病变5例，滤泡性病变2例，滤泡性肿瘤2例。比较初次诊断为良性病变和恶性病变患者的甲状腺FNAC检查标本中miR-221、miR-222表达水平。以术后病理检查结果为金标准，绘制甲状腺FNAC检查标本中miR-221、miR-222诊断恶性甲状腺结节的受试者工作特征曲线（ROC曲线），并计算ROC曲线下面积（AUC），最佳截断值、灵敏度、特异度。计算甲状腺FNAC检查结果联合甲状腺FNAC检查标本中miR-221、miR-222诊断甲状腺结节的符合率。并比较不同一般资料患者甲状腺FNAC检查标本中miR-221、miR-222表达水平。结果　60例患者经甲状腺术后病理检查示，良性结节51例，恶性结节9例。恶性结节患者FANC检查中miR-221、miR-222表达水平高于良性结节患者（P<0.05）。甲状腺FNAC检查标本中miR-221诊断恶性甲状腺结节的AUC为0.774（0.691，0.858），其最佳截断值为2.77，灵敏度为80%，特异度为60.0%，约登指数为0.400。甲状腺FNAC检查标本中miR-222诊断恶性甲状腺结节的AUC为0.759（0.672，0.845），其最佳截断值为2.73，灵敏度为76.7%，特异度为66.7%，约登指数为0.443。甲状腺FNAC检查结果联合甲状腺FNAC检查标本中miR-221、miR-222诊断甲状腺结节与术后病理检查结果的符合率为80.0%。不同性别、年龄、肿瘤最大径、病灶数量、包膜侵犯情况、淋巴结转移情况、TNM分期患者miR-221、miR-222表达水平比较，差异无统计学意义（P>0.05）。结论　恶性甲状腺患者甲状腺FNAC检查标本中miR-221、miR-222表达水平明显升高，其单独鉴别良恶性甲状腺结节的诊断价值不高，但联合甲状腺FNAC检查结果可以提高对良恶性甲状腺结节的诊断效能。

关键词: 甲状腺结节；微RNAs；miR-221；miR-222；甲状腺细针穿刺；诊断, 鉴别