Dickkopf-1在肝内胆管细胞癌组织及血清中的表达及其临床意义

Expression and Clinical Significance of Dickkopf-1 in Tissue and Serum Samples of Intrahepatic Cholangiocarcinoma

目的:探讨Dickkopf-1(DKK1)在肝内胆管细胞癌组织及血清中的表达及其临床意义。方法:应用即时聚合酶链锁反应(qRT-PCR)检测16例肝内胆管细胞癌及其癌旁组织标本中DKK1的表达;应用酶联接免疫吸附试验(ELISA)方法检测15例肝内胆管细胞癌患者术前血清及20例健康志愿者中DKK1的表达;应用免疫组织化学检测50例胆管癌组织中DKK1的表达,分析DKK1与临床特征的关系。结果:16例肝内胆管细胞癌组织中DKK1mRNA的表达显著高于癌旁组织(P<0.05),ELISA检测显示胆管细胞癌患者术前血清中DKK1含量显著高于正常对照组(P<0.05)。免疫组织化学检测显示DKK1阳性表达率为38%(19/50),且DKK1表达程度与肿瘤包膜、血管侵犯、肝门淋巴结转移、TNM分期密切相关,肿瘤无包膜、有血管侵犯、有肝门淋巴结转移和TNM分期III～IV的患者中DKK1表达显著上调(P<0.05)。结论:DKK1高表达与肝内胆管细胞癌的肿瘤恶性表型相关,DKK1可能参与肿瘤侵袭和转移。血清DKK1有望作为肝内胆管细胞癌的血清学诊断指标。

Objective：To study the expression of Dickkopf-1（DKK1） in tissue and serum samples from patients with intrahepatic cholangiocarcinoma and its relationship with clinical features.Methods：Expression of DKK1 mRNA in 16 cases of intrahepatic cholangiocarcinoma was detected by quantitative real-time polymerase chain reaction（qRT-PCR）.Serum levels of DKK1 in 15 intrahepatic cholangiocarcinoma patients before operation and 20 healthy volunteers were measured by enzyme-linked immunosorbent assay（ELISA）.Expression of DKK1 was further analyzed by immunohistochemistry in tumor samples from 50 cases of intrahepatic cholangiocarcinoma.Finally,the relationships between DKK1 expression and clinical characteristics were analyzed.Results： In 16 cases of intrahepatic cholangiocarcinoma,DKK1 mRNA levels were significantly higher in tumor tissues than in peritumoral tissues（P〈0.05）.ELISA showed the serum levels of DKK1 were significantly higher in intrahepatic cholangiocarcinoma patients preoperatively than in healthy volunteers.DKK1 expression levels were higher in tumors without encapsulation and tumor with vascular invasion and hilar lymph node metastasis（P〈0.05）.Conclusions： The overexpression of DKK1 is correlated with malignant phenotype of intrahepatic cholangiocarcinoma and DKK1 probably implicates in tumors invasion and metastasis.Serum DKK1 has the potential to be a diagnostic marker for intrahepatic cholangiocarcinoma.