摘要目的:探讨趋化因子在分化型甲状腺癌(DTC)患者血清中的表达水平与DTC进展间的关系。方法:回顾性收集2017年1月至2017年4月间同济大学附属第十人民医院核医学科的76例DTC术后患者(男25例、女51例，中位年龄39岁)外周血血样，检测其中40种趋化因子水平。以不同方式对患者进行分组：(1)按照是否发生转移，分为非转移组( n＝13)和转移组( n＝63)；(2)按照DTC失分化程度，分为未转移组( n＝13)、仅淋巴结转移组( n＝48)、高度恶性组( n＝11)和碘难治性DTC(RAIR－DTC)伴远处转移组( n＝4)；(3)按照患者近2年随访 131I治疗次数，分为单次治疗组( n＝51)与多次治疗组( n＝25)。比较各组间趋化因子的水平差异；采用受试者工作特征(ROC)曲线分析评价有差异的趋化因子水平预测DTC转移及行多次 131I治疗的效能。采用两独立样本 t检验、Mann－Whitney U检验、单因素方差分析等分析数据。 结果:与非转移组相比，转移组中嗜酸性粒细胞趋化因子3[Eotaxin－3；(25.94±6.05)与(21.76±5.71) ng/L]、γ－干扰素[IFN－γ；(116.04±28.98)和(98.71±26.18) ng/L]、巨噬细胞衍生趋化因子[MDC；(1 468.08±401.74)和(1 082.94±423.30) ng/L]及胸腺表达趋化因子[TECK；505.22(419.80，563.36)和402.89(347.43，442.97) ng/L]的表达降低( t值：2.376、2.131、3.007， U＝215.000，均 P<0.05)。采用IFN－γ＋MDC＋TECK预测甲状腺癌转移的ROC曲线下面积为0.844(95% CI: 0.755～0.932， P<0.001)，灵敏度为79.37%(50/63)。未转移组、仅淋巴结转移组、高度恶性组和RAIR－DTC伴远处转移组间仅MDC的差异有统计学意义[(1 468.08±401.74)、(1 121.59±454.20)、(976.07±281.04)和(922.68±342.41) ng/L; F＝3.564， P<0.05]，且随失分化程度增加MDC水平逐渐降低。与单次治疗组相比，多次治疗组中仅白介素(IL)－8的水平升高[28.20(23.22，32.51)与30.51(26.98，35.57) ng/L； U＝801.000， P<0.05]；IL－8预测行多次 131I治疗的ROC曲线下面积为0.648(95% CI：0.523～0.773， P<0.05)，灵敏度达100%(25/25)。 结论:在DTC中，IFN－γ、MDC及TECK水平降低可能是预测肿瘤发生转移的潜在标志；MDC很可能是DTC失分化的潜在分子靶标，其表达降低可能预示肿瘤失分化的恶性程度增加；IL－8或可用于预测患者是否需行多次 131I治疗。

abstractsObjective:To investigate the relationship between the expression levels of chemokines in serum of patients with differentiated thyroid carcinoma (DTC) and the progression of DTC.Methods:From January to April in 2017, blood samples of 76 patients (25 males, 51 females, median age: 39 years) with DTC after surgery in Nuclear Medicine Department of Tenth People′s Hospital Affiliated to Tongji University were collected retrospectively for detecting the expression levels of 40 chemokines. Patients were divided into different groups according to (1) with or without metastasis: the non-metastasis group ( n=13) and the metastasis group ( n=63); (2) degree of gradual dedifferentiation: without metastasis group ( n=13), lymph node metastasis group ( n=48), highly malignant group ( n=11) and radioactive iodine refractory (RAIR) with distant metastasis group ( n=4); (3) frequency of 131I treatment in follow-up for nearly 2 years: single treatment group ( n=51) and multiple treatment group ( n=25). Differences in chemokine levels among groups were compared. Receiver operating characteristic (ROC) curve analysis was used to evaluate the predictive value of differential chemokines′ levels on DTC metastasis and multiple 131I treatment. Independent-sample t test, Mann-Whitney U test and one-way analysis of variance were used to analyze the data. Results:Compared with the non-metastatic group, the expression levels of Eotaxin-3 ((25.94±6.05) vs (21.76±5.71) ng/L), interferon-γ (IFN-γ; (116.04±28.98) vs (98.71±26.18) ng/L), macrophage-derived chemokine (MDC; (1 468.08±401.74) vs (1 082.94±423.30) ng/L) and thymus expressd chemokine (TECK; (505.22(419.80, 563.36) vs 402.89(347.43, 442.97) ng/L) in metastatic group were decreased, and the differences were statistically significant ( t values: 2.376, 2.131, 3.007, U=215.000, all P<0.05). The area under the ROC curve of IFN-γ+ MDC+ TECK for predicting DTC metastasis was 0.844(95% CI: 0.755-0.932, P<0.001), and the sensitivity was 79.37%(50/63). Only the differences of MDC among without metastasis group, lymph node metastasis group, highly malignant group and RAIR with distant metastasis group were significant ((1 468.08±401.74), (1 121.59±454.20), (976.07±281.04), (922.68±342.41) ng/L; F=3.564, P<0.05), and the expression was gradually decreased with the degree of dedifferentiation. Only IL-8 was significantly increased in the multiple treatment group compared with the single treatment group (28.20(23.22, 32.51) vs 30.51(26.98, 35.57) ng/L; U=801.000, P<0.05). The area under the ROC curve of IL-8 for predicting multiple 131I treatment was 0.648(95% CI: 0.523-0.773, P<0.05), and the sensitivity was 100%(25/25). Conclusions:Decreased expression of IFN-γ, MDC and TECK may be potential markers for predicting metastasis in DTC. MDC is likely to be a potential molecular target for detecting the dedifferentiation degree of DTC, decreased expression of which may indicate the increased malignancy of tumor. IL-8 may be used to predict whether patients need multiple 131I treatments.