甲状腺乳头状癌血浆和癌组织中DKK1的表达及临床意义

Expression and clinical significance of plasma and tissue DKK1 in human papillary thyroid carcinoma

目的本研究旨在通过检测甲状腺乳头状癌(papillary thyroid carcinoma,PTC)患者血浆和癌组织中的DKK1表达情况,分析其与临床病理参数及β-catenin表达间的关系,探讨DKK1与PTC发生、发展的相关性。方法纳入2017年1月至2019年12月在承德医学院附属医院甲状腺外科进行手术治疗的80例PTC患者和100例健康对照者,取患者PTC组织和癌旁组织,并留取患者和健康对照者的清晨空腹静脉血。采用酶联免疫吸附法检测血浆分泌型蛋白Dickkopf-1(DKK1)和β-catenin浓度,采用免疫组织化学法检测组织DKK1和β-catenin表达。结果PTC患者的血浆DKK1水平显著低于健康对照者(t=5.863,P<0.001),而血浆β-catenin水平显著高于健康对照(t=6.223,P<0.001),且患者血浆DKK1和β-catenin水平呈负相关(r=-0.724,P<0.001);PTC组织的DKK1阳性表达率显著低于癌旁组织(χ2=44.545,P<0.001),而β-catenin阳性表达率显著高于癌旁组织(χ2=26.243,P<0.001),且PTC组织中DKK1和β-catenin表达呈负相关(χ2=13.637,P<0.001),关联系数为-0.413。PTC患者的血浆DKK1水平与疾病分期(t=3.040,P=0.003)和是否有淋巴结转移(t=5.452,P<0.001)有关,PTC组织DKK1阳性表达率也与是否发生淋巴结转移有关(χ2=7.486,P=0.006)。此外,使用血浆DKK1水平对PTC进行诊断的曲线下面积(area under curve,AUC)为0.821(95%CI=0.750~0.892,P=0.002)。结论血浆和组织中DKK1表达下调与PTC的发生、发展有关,具有一定的临床应用价值。

Objective To detect the expression of DKK1 in plasma and cancer tissues of patients with papillary thyroid carcinoma(PTC),to analyze its relationship with clinicopathological parameters andβ-catenin expression,and to explore the occurrence and development of DKK1 and PTC relevance.Methods 80 patients with PTC undergoing surgical treatment in Department of Thyroid Surgery,the Affiliated Hospital of Chengde Medical University from Jan.2017 to Dec.2019 and 100 healthy controls were included in the study.PTC tissues and paracancerous tissues of the patients were taken,and the morning fasting venous blood of the patients and healthy controls were retained.The concentrations of DKK1 andβ-Catenin in plasma were detected by enzyme-linked immunosorbent assay,and the expression of DKK1 andβ-Catenin in tissue was detected by immunohistochemistry.Results The plasma DKK1 level of PTC patients was significantly lower than that of healthy controls(t=5.863,P<0.001),while the plasmaβ-catenin level was significantly higher than that of the healthy controls(t=6.223,P<0.001),and the plasma DKK1 andβ-catenin levels of PTC patients were negatively correlated(r=-0.724,P<0.001);the positive expression rate of DKK1 in PTC tissues was significantly lower than that in paracancerous tissues(χ2=44.545,P<0.001),while the positive expression rate ofβ-catenin was significantly lower than that in paracancerous tissues(χ2=44.545,P<0.001).The positive expression rate of DKK1 andβ-catenin in PTC was significantly higher than that in paracancerous tissues(χ2=26.243,P<0.001),and the expression of DKK1 andβ-catenin in PTC was negatively correlated(χ2=13.637,P<0.001).The level of plasma DKK1 in PTC patients was related to disease stage(t=3.040,P=0.003)and lymph node metastasis(t=5.452,P<0.001).The positive expression rate of DKK1 in PTC tissue was also related to lymph node metastasis(χ2=7.486,P=0.006).In addition,the area under curve(AUC)of the diagnostic effect of plasma DKK1 level on PTC was 0.821(95%CI=0.750-0.892,P=0.002).Conclusion The down-regulation of DKK1 expression in plasma and tissue is related to the occurrence and development of PTC,which has certain clinical application value.