基于血浆循环游离DNA与甲状腺结节超声特征构建甲状腺癌诊断模型及其验证  

Establishment of diagnosis model for thyroid cancer based on plasma circulating cell-free DNA and ultrasound characteristic of thyroid nodules and its verification

作　　者：余幼林 沈雄山[1] 胡超华[1] 余军林 卢婷 杨峰 张文杰[1] 张小莉[1] 刘汉忠 陶溢潮 YU Youlin;SHEN Xiongshan;HU Chaohua;YU Junlin;LU Ting;YANG Feng;ZHANG Wenjie;ZHANG Xiaoli;LIU Hanzhong;TAO Yichao(Department of Thyroid and Breast Surgery,Xiaogan Hospital Affiliated to Wuhan University of Science and Technology,Xiaogan,Hubei 432000,China;Department of Oncology,Xiaogan Hospital Affiliated to Wuhan University of Science and Technology,Xiaogan,Hubei 432000,China;Department of Pathology,Xiaogan Hospital Affiliated to Wuhan University of Science and Technology,Xiaogan,Hubei 432000,China;Department of Ultrasound Imaging,Xiaogan Hospital Affiliated to Wuhan University of Science and Technology,Xiaogan,Hubei 432000,China;JJinzhou Medical University,Jinzhou,Liaoning 121000,China)

机构地区：[1]武汉科技大学附属孝感医院甲状腺乳腺外科,湖北孝感432000 [2]武汉科技大学附属孝感医院肿瘤科,湖北孝感432000 [3]武汉科技大学附属孝感医院病理科,湖北孝感432000 [4]武汉科技大学附属孝感医院超声科,湖北孝感432000 [5]锦州医科大学,辽宁锦州121000

出　　处：《中国普通外科杂志》2021年第8期955-963,共9页China Journal of General Surgery

基　　金：湖北省卫生健康科研基金资助项目(WJ2018H0098);武汉科技大学附属孝感医院(孝感市中心医院)院级科研基金资助项目(201818)。

摘　　要：背景与目的:研究显示,血浆循环游离DNA(cfDNA)可能是甲状腺癌诊断的潜在生物标志物,因此,本研究探讨以血浆循环cfDNA和甲状腺结节超声特征性改变建立的评分模型用于甲状腺良恶性结节鉴别诊断中的价值。方法:以2018年6月—2020年10月期间收治甲状腺结节患者240例为研究对象(甲状腺癌132例,良性甲状腺结节108例),按照1∶1比例随机分为建模组和验证组。用血液DNA提取试剂盒提取240例患者的血浆cfDNA,进一步用qRT-PCR检测DNA的浓度,同时对所有患者进行超声检查。基于患者cfDNA浓度,甲状腺结节超声的改变构建评分模型,分析其在甲状腺癌诊断中的敏感度、特异度、阳性预测值、阴性预测值,并在验证组中验证模型的有效性。结果:甲状腺癌患者的cfDNA浓度明显高于良性结节患者(P<0.001)。单因素分析结果显示,cfDNA浓度及超声影像特征(纵横比、内部回声、包膜完整性、钙化、囊性病变)在良恶性结节患者中差异有统计学意义(均P<0.05);多因素Logistic回归分析结果表明,cfDNA≥56.84 ng/mL,以及超声显示纵横比≥1、包膜不完整性、低回声、钙化、非囊性病变是诊断甲状腺癌的独立危险因素(均P<0.05);用以上变量的标准回归系数建立了评分模型,该模型诊断甲状腺癌的ROC曲线下面积(AUC)为0.958(95%CI=0.926~0.989),最佳截断值为5.5,其诊断敏感度、特异度、阳性预测值、阴性预测值分别为85.5%、89.7%、89.8%、85.2%,均优于单一指标的预测效能。验证结果显示,验证组中AUC为0.902(95%CI=0.848~0.957)。结论:基于血浆cfDNA和甲状腺结节超声特征性的评分系统对甲状腺癌的诊断中具有较高的预测价值,为甲状腺良恶性结节鉴别诊断提供参考。当甲状腺结节评分≥5.5时预示应积极临床干预。Objective:Studies have demonstrated that the circulating cell-free DNA(cfDNA)may be a potential biomarker for diagnosis of thyroid cancer.Therefore,this study was performed to investigate the value of a scoring model established by plasma circulating cfDNA and changes in ultrasound characteristics of the thyroid nodules in differential diagnosis between benign and malignant thyroid nodules.Methods:Two hundred and forty patients with thyroid nodules(132 cases of thyroid cancer and 108 cases of benign thyroid nodules)admitted from June 2018 to October 2020 were enrolled for this study.They were randomly divided into the modeling group and validation group using a 1∶1 ratio.The plasma cfDNAs were extracted from the 240 patients by blood DNA extraction kit,and the DNA concentrations were further detected by q RT-PCR.Thyroid ultrasound was performed in all patients.The scoring model was constructed based on the cfDNA concentration and thyroid ultrasound characteristics,and then,its sensitivity,specificity,positive predictive value and negative predictive value for diagnosis of thyroid cancer were analyzed.The effectiveness of the model was evaluated in the validation group.Results:The cfDNA concentration in patients with thyroid cancer was significantly higher than that in patients with benign nodules(P<0.001).The results of univariate analysis showed that there were significant differences in cfDNA concentration and ultrasound imaging features that included the aspect ratio,internal echo,integrity of the capsule,calcification and cystic lesions between patients with malignant and benign nodules(all P<0.05).The results of multivariate Logistic regression analysis showed that cfDNA≥56.84 ng/mL,and thyroid ultrasound presenting the aspect ratio≥1,incomplete capsule,hypoechoic,calcification,and non-cystic lesions were independent risk factors for diagnosis of thyroid cancer(all P<0.05).According to the standard regression coefficients of above variables,a scoring model was established.The area under the ROC curve(A

关 键 词：甲状腺肿瘤 循环肿瘤DNA 超声检查 诊断 鉴别 

分 类 号：R736.1[医药卫生—肿瘤]