1、1现代检验医学杂志第 38 卷第 1 期2023 年 1 月J Mod Lab Med,Vol.38,No.1,Jan.2023甲状腺乳头状癌患者术前血清 TK1 表达水平联合 甲状腺超声特征构建中央区淋巴结转移预测模型及验证宋晓龙，魏龙，秦晋铝，杨茹，周建平（陕西省人民医院放免中心，西安 710068）摘要：目的探讨血清胸苷激酶 1(serum thymidine kinase 1,sTK1)联合甲状腺超声特征预测甲状腺乳头状癌（papillary thyroid carcinoma，PTC）患者中央区淋巴结转移（central lymph node metastasis,CLNM）的风险。
2、方法选取 2020 年10 月 2021 年 12 月陕西省人民医院确诊的 CLNM 的 PTC 患者 110 例为观察组，同期无 CLNM 的 PTC 患者 104 例为对照组。所有患者行甲状腺超声检查，检测 sTK1 等指标水平，采用 t 检验比较两组间 sTK1 等指标的水平差异，卡方检验分析颈部超声结果的差异，Logistic 回归分析 CLNM 的独立危险因素，构建列线图预测模型，并选取 2022 年15 月陕西省人民医院确诊的 80 例 PTC 患者对模型的预测准确度进行外部验证。结果观察组 sTK1 水平高于对照组（2.060.75pmol/L vs 1.590.66pmol/L
3、），差异有统计学意义（t=4.75，P 0.05）。sTK1 预测 PTC 患者 CLNM 的曲线下面积（AUC）为 0.678，截断值为 1.50 pmol/L，灵敏度和特异度分别为 79.1%，61.0%。单因素分析结果显示，sTK1 1.5 pmol/L，边界不清、结节微钙化、肿瘤数目、肿瘤直径 1cm 和淋巴结明显血流信号是 PTC 患者 CLNM 的独立风险因素（2=5.2426.72，均 P 1、肿瘤位置与 CLNM 无关（2=0.277.16，均 P 0.05）。基于上述危险因素构建预测模型并进行准确度验证，采用建模原始数据进行内部验证 AUC 为 0.826，验证队列进行外部验
4、证 AUC 为 0.809，表明该模型具有一定的预测准确度。结论PTC 患者术前 sTK1 表达水平联合甲状腺超声特征构建 CLNM 预测模型具有一定的临床应用价值，当 sTK1 1.5 pmol/L，边界不清、结节微钙化、肿瘤多灶、肿瘤直径 1cm，淋巴结有明显血流信号时，发生 CLNM 的概率较高，建议行预防性中央区淋巴结清扫术。关键词：甲状腺乳头状癌；血清胸苷激酶；中央区淋巴结；预测模型中图分类号：R736.1；R730.43文献标识码：A文章编号:1671-7414（2023）01-001-06doi:10.3969/j.issn.1671-7414.2023.01.001Constr
5、uction and Validation of Prediction Model of Central Lymph Node Metastasis in Patients with Papillary Thyroid Carcinoma Based on Preoperative Serum TK1 Expression Level and Thyroid Ultrasound FeaturesSONG Xiao-long,WEI Long,QIN Jin-l,YANG Ru,ZHOU Jian-ping(Radiation and Immunization Center,Shaanxi P
6、rovincial Peoples Hospital,Xian 710068,China)Abstract:ObjectiveTo explore the prediction of the risk of central lymph node metastasis(CLNM)in patients with papillary thyroid carcinoma(PTC)by serum thymidine kinas 1(sTK1)combined with thyroid ultrasound features.MethodsFrom October 2020 to December 2
7、021,110 PTC patients with CLNM diagnosed by Shaanxi Provincial Peoples Hospital were selected as the observation group,and 104 PTC patients without lymph node metastasis in the central region were selected as the control group.All patients were examined by thyroid ultrasound and the level of sTK1 an
8、d other indicators were detected.The difference of 104 PTC patients without lymph node metastasis in the ceatral region were selected as the control group,and other indicators between the two groups was compared by t-test,the difference of neck ultrasound results was analyzed by Chi square test(2 te
9、st),and the independent risk factors of CLNM were analyzed by logistic regression.A nomogram prediction model was constructed.80 PTC patients diagnosed by Shaanxi Provincial Peoples Hospital from January 2022 to May 2022 were selected for external verification of the prediction accuracy of the model
10、.ResultsThe level of sTK1 in the observation group was higher than that in the control group（2.060.75pmol/L vs 1.590.66pmol/L）,and the difference was statistically significant(t=4.75,P0.05).The area under the curve(AUC)predicted by sTK1 for CLNM in PTC patients was 0.678,基金项目：陕西省科技厅一般项目（2021SF-069）。
11、作者简介：宋晓龙（1988-），女，硕士，主管检验技师，主要研究方向：临床检验诊断学，E-mail：zixuan_。通讯作者：周建平（1974-），男，硕士，副主任医师，主要从事肿瘤早期筛查和诊断工作，E-mail:。2现代检验医学杂志第 38 卷第 1 期2023 年 1 月J Mod Lab Med,Vol.38,No.1,Jan.2023the cut-off value was 1.50 pmol/L,and the sensitivity and the specificity was 79.1%,61.0%,respectively.The results of univariat
12、e analysis showed that sTK1 1.5 pmol/L,unclear boundary,nodule microcalcifications,tumor number,tumor diameter1cm and obvious blood flow signal of lymph nodes were independent risk factors of CLNM in PTC patients(2=5.2426.72,all P1,and tumor location were not related to CLNM(2=0.277.16,all P0.05).Ba
13、sed on the above risk factors,a prediction model was built and its accuracy was verified.The AUC of the internal verification using the modeling raw data was 0.826,and the AUC of the external verification using the verification queue was 0.809,which indicates that the model had a certain prediction
14、accuracy.ConclusionThe expression of sTK1 in PTC patients before operation combined with the characteristics of thyroid ultrasound to construcs a prediction modesl of CLNM has certain clinical application value.When sTK11.5 pmol/L,irregular edges,microcalcifications,multiple tumors,tumor diameter1 c
15、m,and lymph nodes had obvious blood flow signals,the probability of CLNM is much higher.It is recommended to perfrom preventive lymph node dissection the central region.Keywords:papillary thyroid carcinoma;serum thymidine kinase 1;central lymph node;prediction model甲状腺癌是人群常见的恶性肿瘤1，其中甲状腺乳头状癌（papillar
16、y thyroid carcinoma，PTC）是最常见的病理类型，约占甲状腺癌的 80%85%2。PTC 患者大部分预后良好，10 年生存率超过90%。但仍有 20%50%的患者会发生颈部淋巴结转移，从而导致复发率升高和生存率降低3。中央区（区）淋巴结是甲状腺癌转移的常见部位，术前超声发现中央区淋巴结转移（certral lymph node metastasis,CLNM）的漏诊率较高，且 PTC 患者是否需行预防性颈部淋巴结清扫以及清扫范围尚有争议4，因此 PTC 患者术前明确颈部淋巴结的转移情况对治疗效果具有重要意义。血清胸苷激酶1(serum thymidine kinase 1,sTK1)是一种肿瘤细胞增殖指标，在多种恶性肿瘤中呈高表达5，与肿瘤转移、复发也有一定相关性。列线图（Nomogram图）可将复杂的多因素回归方程转变为可视化图形，有利于对患者进行评估，在临床实践中应用较 多6-7。有研究报道基于 CT 影像组学建立列线图用以鉴别甲状腺滤泡性肿瘤的良恶性8，但以列线图作为 CLNM 的预测工具还少有报道。本研究拟分析 PTC 患者的 sTK1，促甲状腺激素（thyr
