血清肝素结合生长因子对分化型甲状腺肿瘤诊断及临床预后的评估价值

Diagnosis and prognosis prediction value of serum midkine in differentiated thyroid cancer

目的:探讨血清肝素结合生长因子(MK)对分化型甲状腺肿瘤诊断及临床预后的评估价值。方法:选择91例分化型甲状腺肿瘤患者(DTC组)、119例甲状腺良性结节患者(良性组)和80例健康人群(对照组)作为研究对象,采用化学发光免疫分析法检测各组游离三碘甲状腺原氨酸(FT3)、游离甲状腺素(FT4)、促甲状腺激素(TSH)、甲状腺球蛋白(Tg)水平,酶联免疫吸附法检测血清MK水平。85例DTC患者获得24个月以上随访,按照随访结果分为清甲成功且无转移病灶(预后良好组)64例和清甲成功但存在转移病灶(预后不良组)21例,分析2组患者无转移生存率,利用受试者工作曲线(ROC)研究血清Tg、MK对DTC诊断价值和转移病灶的预测价值。结果:DTC组血清Tg、MK显著高于良性组和对照组(P<0.05),良性组血清Tg显著高于对照组(P<0.05);预后不良组血清FT3、FT4、Tg、MK显著高于预后良好组(P<0.05)。在最佳临界值(Tg=25.31mg/L,MK=0.33ng/L)时,MK诊断DTC的敏感度为78.7%,特异度为81.3%,AUC为0.848(95%CI:0.791~0.905,P<0.05),MK诊断DTC的AUC高于Tg(AUC:0.787,95%CI:0.712~0.861,P<0.05);在最佳临界值(Tg=30.18mg/L,MK=0.71ng/L)时,MK预测DTC转移的敏感度为74.7%,特异度为88.3%,AUC为0.971(95%CI:0.951~0.991,P<0.05),MK预测DTC转移的AUC高于Tg(AUC:0.868,95%CI:0.811~0.925,P<0.05)。相关性分析显示,血清Tg与MK呈正相关关系(r=0.816,P<0.05),Tg与年龄呈正相关关系(r=0.913,P<0.05),MK与年龄呈正相关关系(r=0.778,P<0.05),其余各指标间均差异无统计学意义(P>0.05)。生存分析显示Tg>30.18mg/L患者24个月无转移生存率为32.7%,Tg≤30.18mg/L患者24个月无转移生存率为83.5%,差异有统计学意义(χ2=78.041,P<0.05)。MK>0.71ng/L患者24个月无转移生存率为51.2%,MK≤0.71ng/L患者24个月无转移生存率为90.6%,差异有统计学意义(χ~2=83.104,P<0.05)。结论:血清MK对DTC的诊断价值和转移病灶的预测价值均高于Tg。

Objective：To explore the diagnosis and prognosis prediction value of serum midkine（MK）in differentiated thyroid cancer.Method：A total of 91 cases of differentiated thyroid cancer patients（DTC group）,119 cases of benign thyroid nodules patients（benign group）and 80 cases of healthy people（control group）were selected as research object,the 3ml of elbow vein blood was extracted from each group,the serum level of free triiodothyronine（FT3）,free thyroxine（FT4）,thyroid stimulating hormone（TSH）,thyroglobulin（Tg）were detected by chemiluminescence immunoassay,and the serum MK level was detected by enzyme-linked immunosorbent assay.Eighty-five cases of DTC patients were followed up for more than 24 months.According to the results of follow-up,85 cases of DTC patients were divided into metastasis free patients（good prognosis group）64cases and metastatic lesions patients（poor prognosis group）21cases.The metastasis free survival rate was analyzed,and the diagnosis of DTC and the predictive value of metastatic lesions were performed by ROC curves.Result：The serum level of Tg and MK in DTC group were significantly higher than those in benign group and control group（P〈0.05）,while serum Tg level in benign group were significantly higher than that in control group（P〈0.05）.The serum level of Tg and MK in poor prognosis group were significantly higher than those in good prognosis group（P〈0.05）.The optimal cut-off value of MK as an indicator for DTC diagnosis was projected to be0.33ng/L,which yielded a sensitivity of 78.7%and a specificity of 81.3%,with an area under the curve（AUC）of 0.848（95%CI：0.791-0.905,P〈0.05）,the AUC of MK diagnosis DTC was higher than that of Tg（AUC：0.787,95%CI：0.712-0.861,P〈0.05）.The optimal cut-off value of MK as an indicator for DTC predict metastases was projected to be 0.71ng/L,which yielded a sensitivity of 74.7%and a specificity of 88.3%,with an area under the curve（AUC）of 0.971（95%CI：0.951-0.991,P〈0.05）,the AUC of MK predict metastase of DTC was higher than that of Tg（AUC：0.868,95%CI：0.811-0.925,P〈0.05）.Correlation analysis showed that serum Tg was positively correlated with MK（r=0.816,P〈0.05）,Tg positive correlated with age（r=0.913,P〈0.05）,MK positive correlated with age（r=0.778,P〈0.05）,there were no significant correlation between other indexes（P〈0.05）.Survival analysis showed that 24 months of metastasis free survival rate was32.7%in Tg30.18mg/L,while metastasis free survival rate was 83.5%in Tg≤30.18mg/L,the difference was statistically significant（χ～2=78.041,P〈0.05）.24 months of metastasis free survival rate was 51.2%in MK0.71ng/L,while metastasis free survival rate was 90.6%in MK≤0.71ng/L,the difference was statistically significant（χ～2=83.104,P〈0.05）.Conclusion：The diagnosis and prognosis prediction value of serum MK might be higher than Tg in DTC.