甲状腺乳头状癌中Dickkopf-1蛋白的表达及与上皮-间质转化的关系  

Expression of Dickkopf-1 protein and its relationship with epithelial-mesenchymal transition in papillary thyroid carcinoma

作　　者：孙敏 凡龙云 江冬瑞[1] 虞红珍[1] 王弦[1,2] 吴强[1,2] SUN Min;FAN Long-yun;JIANG Dong-rui;YU Hong-zhen;WANG Xian;WU Qiang(Department of Pathology,the Second Affiliated Hospital of Anhui Medical University,Hefei 230601,China;Department of Pathology,Anhui Medical University,Hefei 230032,China)

机构地区：[1]安徽医科大学第二附属医院病理科,合肥230601 [2]安徽医科大学基础医学院病理学教研室,合肥230032

出　　处：《临床与实验病理学杂志》2023年第3期275-280,共6页Chinese Journal of Clinical and Experimental Pathology

基　　金：安徽省高校自然科学研究重点项目(KJ2020A0183);安徽省高校优秀青年人才支持计划项目(gxyq2021177);安徽医科大学第二附属医院临床研究培养计划(2020LCYB14)。

摘　　要：目的探讨甲状腺乳头状癌(papillary thyroid carcinoma,PTC)和甲状腺乳头状增生(papillary thyroid hyperplasia,PTH)中Dickkopf-1(DKK1)的表达及与上皮-间质转化(epithelial-mesenchymal transition,EMT)相关蛋白的关系。方法采用生物信息学技术分析TCGA数据库中DKK1在PTC中的诊断价值;采用免疫组化EnVision法检测80例PTC和60例PTH组织中DKK1蛋白的表达,以及PTC组织中MMP-2、E-cadherin和vimentin的表达,并分析其与临床病理特征及相关性。结果生物信息学分析和免疫组化结果显示,DKK1对PTC诊断预测的曲线下面积(AUC)分别为0.674和0.874(P均<0.001),其灵敏度为95.0%,特异性为71.2%,诊断准确度为81.4%,误诊率为28.8%,漏诊率为5.0%,具有较高的诊断价值。PTC和PTH组织中DKK1的阳性率分别为28.8%(23/80)和95.0%(57/60),差异有统计学意义(P<0.001)。DKK1、MMP-2和E-cadherin表达与淋巴结转移相关(P<0.05),vimentin表达与淋巴结转移和患者年龄相关(P<0.05)。PTC组织中DKK1表达与E-cadherin表达呈正相关(rs=0.272,P<0.05),与MMP-2、vimentin表达均呈负相关(rs=-0.335、-0.336,P均<0.05)。结论DKK1可作为辅助PTC和PTH鉴别诊断的重要标志物;DKK1可能参与PTC的EMT过程,可作为预测PTC侵袭和淋巴结转移的潜在标志物。Purpose To explore Dickkopf-1(DKK1)expression in papillary thyroid carcinoma(PTC)and papillary thyroid hyperplasia(PTH),and to investigate its relationship with epithelial-mesenchymal transition(EMT)related proteins.Methods Bioinformatics analysis was used to detect the diagnostic value of DKK1 in PTC in the TCGA database.Immunohistochemistry was used to detect the expression of DKK1 protein in 80 cases of PTC and 60 cases of papillary thyroid hyperplasia(PTH).Meanwhile,the expression of MMP-2,E-cadherin and vimentin proteins in PTC was also detected.Then their clinicopathological significance,and the relationship were analyzed between each other.Results The bioinformatics results and immunohistochemistry showed that the area under the curve prediction(AUC)of DKK1 for PTC diagnosis was 0.674 and 0.874 respectively(P all<0.001),the expression of DKK1 showed a sensitivity of 95.0%,specificity of 71.2%,diagnostic accuracy of 81.4%,misdiagnosis rate of 28.8%,and missed diagnosis rate of 5.0%,suggesting that DKK1 had diagnostic value in PTC.Immunostaining results showed that the positive rate of DKK1 was 28.8%(23/80)in PTC tissues,while 95.0%(57/60)in PTH tissues,which was statistically different(P<0.001).DKK1,MMP-2 and E-cadherin protein were associated with lymph node metastasis(P<0.05),vimentin was associated with lymph node metastasis and age of patients(P<0.05).In addition,a positive correlation between DKK1 and E-cadherin(r s=0.272,P<0.05)was observed in PTC tissues,while DKK1 protein expression was negatively correlated with MMP-2 and vimentin(r s=-0.335,-0.336,P all<0.05).Conclusion DKK1 may be used as an important marker for distinguishing PTC from PTH,and it might be involved in the EMT process of PTC.Therefore,DKK1 may be a valuable potential marker to predict the invasion and lymphnode metastasis of PTC.

关 键 词：甲状腺肿瘤 乳头状癌 乳头状增生 上皮-间质转化 DKK1 

分 类 号：R737.9[医药卫生—肿瘤]