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随着医学科技水平的发展,医学检查方法愈趋多样化、医学仪器设备愈趋高端化,甲状腺结节在健康人群中的检出率也随之升高,达50%~60%[1]。目前细针穿刺活检被认为是术前诊断甲状腺结节良恶性的“金标准”,其诊断灵敏度达83%(65%~98%)、特异度达92%(72%~100%),但仍有15%~20%的患者不能被确诊,在这部分患者中,仅有20%~25%的患者经术后病理结果被诊断为恶性结节,75%~80%的患者接受了不必要的甲状腺手术[2]。另外,目前常用甲状腺球蛋白(thyroglobulin,Tg)水平预测转移情况,但其易受到抗甲状腺球蛋白抗体(thyroglobulin antibody,TgAb)的干扰,且部分术后行131I治疗的DTC患者在治疗中会出现Tg水平较高而全身碘扫描结果显示阴性的情况,这会对临床诊断造成一定的困扰[3-4]。针对这些临床困惑,本研究通过检测血清midkine(MK)和galectine-3(Gal-3)水平来进行补充,以便临床医师更好地制定治疗方案和评估患者的预后。
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根据2次治疗性131I全身扫描结果及期间其他影像学检查结果中是否有淋巴结和(或)肺转移,将51例DTC术后患者分为转移阳性组和转移阴性组,其中转移阳性组8例,包括男性2例、女性6例,年龄25~61(40.41±9.53)岁,具体转移部位见表1;转移阴性组43例,包括男性10例、女性33例,年龄26~72(48.41±10.89)岁。
编号 年龄 性别 转移部位 1 25 女 双侧颈Ⅱ区 2 28 女 左颈Ⅲ区及右颈Ⅵ区 3 33 男 右颈Ⅳ区 4 34 女 右颈Ⅲ、Ⅳ区 5 43 男 双肺多发转移 6 47 女 左颈Ⅵ区及右颈Ⅱ区 7 52 女 右颈Ⅲ、Ⅳ区 8 61 女 双肺多发转移 表 1 分化型甲状腺癌患者术后转移阳性组患者淋巴结和 (或)肺转移部位
Table 1. Locations of lymph node and/or lung metastasis in differentiated thyroid carcinoma positive group
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甲状腺结节恶性组、良性组和健康对照组3组间的年龄差异无统计学意义(F=0.28,P>0.05)。恶性组的血清MK和Gal-3水平均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),但良性组与健康对照组间血清MK和Gal-3水平的差异均无统计学意义(t=−0.90、0.63,均P>0.05)(表2)。
组别 MK(pg/mL) Gal-3(ng/mL) 恶性组(n=23) 385.79±198.62 2.97±1.45 良性组(n=18) 280.12±101.24 1.29±0.33 健康对照组(n=32) 270.93±104.18 1.05±0.39 F值 48.40 5.08 P值 <0.01 0.01 注:表中,MK:midkine;Gal-3:galectine-3 表 2 2组甲状腺结节患者和健康对照者的血清学指标比较 (
±s)$\bar x $ Table 2. Comparison of serological indexes among malignant, benign and healthy thyroid nodules (
±s)$ \bar x$ ROC曲线分析结果显示,MK的最佳阈值为318.87 pg/mL、AUC为0.91(95%CI: 0.81~0.99)、灵敏度为88.5%、特异度为78.1%;Gal-3的最佳阈值为1.61 ng/mL、AUC为0.72(95%CI: 0.57~0.86)、灵敏度为69.8%、特异度为70.4%(图1)。
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转移阳性组的血清MK和Gal-3水平较转移阴性组均明显升高,转移阳性组的Tg水平明显高于转移阴性组,且差异均有统计学意义(t=−4.86~−2.89,均P<0.01)(表3)。
组别 MK(pg/mL) Gal-3(ng/mL) Tg(ng/mL) 转移阳性组
(n=8)489.93±124.69 2.82±1.51 176.30±131.94 转移阴性组
(n=43)277.41±115.24 1.74±0.66 15.10±14.38 t值 −4.01 −2.89 −4.86 P值 <0.01 <0.01 <0.01 注:表中,MK:midkine;Gal-3:galectine-3;Tg:甲状腺球蛋白 表 3 分化型甲状腺癌患者术后首次131I治疗前2组的血清 学指标比较(
±s)$\bar x $ Table 3. Comparison of serum indexes between 2 groups in patients after differentiated thyroid carcinoma before the first 131I treatment (
±s)$\bar x $ -
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(图2)。
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
Diagnostic value of serum MK and Gal-3 in thyroid nodules and postoperative DTC metastases
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摘要:
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。 -
关键词:
- 甲状腺结节 /
- 甲状腺肿瘤 /
- 肿瘤转移 /
- 血清midkine /
- 血清galectine-3
Abstract: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. -
Key words:
- Thyroid nodule /
- Thyroid neoplasms /
- Neoplasm metastasis /
- Serum midkine /
- Serum galectine-3
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表 1 分化型甲状腺癌患者术后转移阳性组患者淋巴结和 (或)肺转移部位
Table 1. Locations of lymph node and/or lung metastasis in differentiated thyroid carcinoma positive group
编号 年龄 性别 转移部位 1 25 女 双侧颈Ⅱ区 2 28 女 左颈Ⅲ区及右颈Ⅵ区 3 33 男 右颈Ⅳ区 4 34 女 右颈Ⅲ、Ⅳ区 5 43 男 双肺多发转移 6 47 女 左颈Ⅵ区及右颈Ⅱ区 7 52 女 右颈Ⅲ、Ⅳ区 8 61 女 双肺多发转移 表 2 2组甲状腺结节患者和健康对照者的血清学指标比较 (
±s)$\bar x $ Table 2. Comparison of serological indexes among malignant, benign and healthy thyroid nodules (
±s)$ \bar x$ 组别 MK(pg/mL) Gal-3(ng/mL) 恶性组(n=23) 385.79±198.62 2.97±1.45 良性组(n=18) 280.12±101.24 1.29±0.33 健康对照组(n=32) 270.93±104.18 1.05±0.39 F值 48.40 5.08 P值 <0.01 0.01 注:表中,MK:midkine;Gal-3:galectine-3 表 3 分化型甲状腺癌患者术后首次131I治疗前2组的血清 学指标比较(
±s)$\bar x $ Table 3. Comparison of serum indexes between 2 groups in patients after differentiated thyroid carcinoma before the first 131I treatment (
±s)$\bar x $ 组别 MK(pg/mL) Gal-3(ng/mL) Tg(ng/mL) 转移阳性组
(n=8)489.93±124.69 2.82±1.51 176.30±131.94 转移阴性组
(n=43)277.41±115.24 1.74±0.66 15.10±14.38 t值 −4.01 −2.89 −4.86 P值 <0.01 <0.01 <0.01 注:表中,MK:midkine;Gal-3:galectine-3;Tg:甲状腺球蛋白 -
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