血清MK和Gal-3水平在甲状腺结节及DTC术后转移灶中的诊断价值

目的 探讨血清midkine（MK）和galectine-3（Gal-3）水平在良恶性甲状腺结节鉴别诊断中的价值，及其在分化型甲状腺癌（DTC）术后患者首次131I治疗前转移灶中的评估价值。 方法 ①甲状腺结节鉴别诊断的回顾性研究:收集2016年11月至2017年11月在山西医科大学第一医院拟行手术治疗的41例甲状腺结节患者男性11例、女性30例，年龄29~73（48.61±11.59）岁]的术前血清样本，根据病理结果分为恶性组（23例）和良性组（18例），同时收集32名健康者作为健康对照组。采用单因素方差分析术前血清MK和Gal-3水平在良恶性甲状腺结节中是否存在差异，并绘制受试者工作特征曲线分析两者对甲状腺结节的诊断价值。②DTC患者术后是否存在转移灶的回顾性研究:收集2016年11月至2017年11月于山西医科大学第一医院核医学科首次服131I治疗前的51例DTC术后患者男性12例、女性39例，年龄25~72（44.41±10.21）岁]的血清样本及临床资料，所有患者行2次131I治疗，并于每次治疗后5~7 d行全身碘扫描，根据其结果及其他检查（超声、CT、PET/CT）结果，判断是否有淋巴结和（或）肺转移。采用两独立样本t检验比较组间血清MK和Gal-3水平的差异性，Pearson检验分析血清MK和Gal-3水平间的相关性。 结果 ①手术前恶性组的血清MK和Gal-3水平明显高于良性组及健康对照组，且差异有统计学意义（F=48.40、5.08，均P<0.05）。对于术前良恶性甲状腺结节的鉴别，MK的最佳阈值为318.87 pg/mL、曲线下面积（AUC）为0.91（95%CI: 0.81~0.99）、特异度为78.1%、灵敏度为88.5%；Gal-3的最佳阈值为1.61 ng/mL、AUC为0.72（95%CI: 0.57~0.86）、特异度为70.4%、灵敏度为69.8%。②51例DTC患者中，转移阳性组8例、转移阴性组43例。转移阳性组甲状腺球蛋白、MK、Gal-3水平均明显高于转移阴性组，且差异有统计学意义（t=?4.86、?4.01、?2.89，均P<0.05）。Pearson相关性分析结果显示，甲状腺结节患者术前（r=0.67，P<0.05）及DTC患者术后（r=0.84，P<0.05）血清MK、Gal-3水平之间均存在显著相关性。 结论 血清MK和Gal-3水平可用于良恶性甲状腺结节的鉴别诊断，并且可以评估DTC术后是否存在肿瘤转移。

Diagnostic value of serum MK and Gal-3 in thyroid nodules and postoperative DTC metastases

Objective To investigate the value of serum midkine (MK) and galectine-3 (Gal-3) in the differential diagnosis of benign and malignant thyroid nodules, and to analyze the ability of serum MK and Gal-3 to evaluate metastases before the first 131I treatment in patients with differentiated thyroid cancer (DTC) after thyroidectomy. Methods ①Data on benign and malignant thyroid nodule differential diagnosis were collected from November 2016 to November 2017 in the First Hospital of Shanxi Medical University. In general surgery, 41 cases (11 males and 30 females, aged 29?73 (48.61±11.59) years) of surgical treatment of thyroid nodules in patients with preoperative blood specimens were determined. The patients were divided according to the result of pathology as follows: malignant group (23 cases) and benign group (18 cases). A total of 32 healthy subjects served as controls. One-way ANOVA was used to analyze whether preoperative serum MK and Gal-3 were different in benign and malignant thyroid nodules. Receiver operating characteristic curve was drawn to study the diagnostic value of the two in thyroid nodules. ②From November 2016 to November 2017, 51 patients (12 males and 39 females, aged 25?72 (44.41±10.21) years) with DTC before the first 131I treatment in the Nuclear Medicine Department of the First Hospital of Shanxi Medical University participated in the evaluation of postoperative metastasis. All patients underwent 131I treatment two times, and the whole body iodine scan was performed 5?7 days after each treatment. According to the results and other examination results (ultrasound, CT, PET/CT), the lymph node and/or lung metastasis was judged. Serum was collected before the first iodine treatment. The differences in MK and Gal-3 between groups were compared using two-sample t-test. Pearson test was used to analyze the correlation between serum MK and Gal-3.before the first iodine treatment. The differences in MK and Gal-3 between groups were compared using two-sample t-test. Pearson test was used to analyze the correlation between serum MK and Gal-3. Results ①Pre-surgical MK and Gal-3 levels were significantly higher in patients with malignant thyroid nodule than those in benign cases and in controls (F=48.40, 5.08, both P<0.05). The ROC curve analysis determined the optimal value of MK and Gal-3 for differential diagnosis between malignant and benign thyroid nodules. The diagnostic power of MK was the highest at 318.87 pg/mL, with an area under the ROC curve (AUC) of 0.91(95%CI: 0.81~0.99), specificity of 78.1%, and sensibility of 88.5%. The diagnostic power of Gal-3 was the highest at 1.61 ng/mL, with AUC of 0.72(95%CI: 0.57~0.86), specificity of 70.4%, and sensibility of 69.8%. ②The patients were grouped according to the presence of lymph node and bone and/or lung metastasis into metastasis positive group (8 cases) and negative group (43 cases). Thyroglobulin, MK(A), and Gal-3(A) in the positive group were significantly higher than those in the negative group (t=?4.86, ?4.01, ?2.89, all P<0.05). MK (r=0.67, P<0.05) and Gal-3 (r=0.84, P<0.05) were significantly correlated in pre-surgical and pre-131I-ablative. Conclusions Serum MK and Gal-3 can be used for the differential diagnosis of benign and malignant thyroid nodules and to evaluate whether metastasis is present in patients with DTC before 131I treatment.