DKK1蛋白表达与肝内胆管细胞癌患者淋巴结侵犯及其预后的相关性研究

The relationship between DKK1 protein expression and lymph node invasion,and prognosis in patients with intrahepatic cholangiocarcinoma

目的探讨DKK1蛋白表达与肝内胆管细胞癌患者淋巴结侵犯及其预后的相关性。方法选择2005年1月—2012年12月来我院行切除治疗肝内胆管癌患者78例,制作肝内胆管细胞癌组织及癌旁组织的组织芯片,并于术前进行生化指标测定。患者术后每隔3个月复查1次,并结合患者的临床资料和病历资料,采用Kaplan-Meier法进行无复发生存曲线及总生存曲线的绘制,采用Cox比例风险回归模型进行多因素分析,确定影响预后无复发生存时间(Relapse-free survival,RFS)和总生存时间(Overall survival,OS)的因素。结果 DKK1蛋白表达阴性与表达阳性的患者间GGT、肝门淋巴结侵犯、Child-Pugh分级、MMP9差异存在统计学意义(P<0.05)。78例肝内胆管细胞癌患者组织芯片结果发现DKK1蛋白在肝内胆管细胞癌的阳性表达率为35.90%(28/78),在癌旁组织中的阳性表达率为14.10%(11/78)。78例肝内胆管细胞癌患者的1、3、5年的总生存率和无复发生存率分别为51.28%(40/78)与50.00%(38/78)、41.03%(32/78)与38.46%(30/78)、25.64%(20/78)与23.08%(18/78)。相关危险性因素经单因素、多因素分析后,研究结果显示GGT、CA19-9、CEA、肿瘤大小、DKK1、肝门淋巴结侵犯是影响肝内胆管细胞癌患者RFS的预后因素;CEA、肿瘤大小、DKK1、肝门淋巴结侵犯是影响肝内胆管细胞癌患者DFS的预后因素。DKK1蛋白表达阳性与阴性的OS与RFS曲线显示,5年后肝内胆管细胞癌患者DKK1蛋白表达阳性与阴性的总生存率分别为28.20%与20.51%;无复发生存率分别为24.36%与21.79%。结论肝内胆管细胞癌患者淋巴结侵犯与否与DKK1蛋白表达密切相关,DKK1蛋白表达可能是影响肝内胆管细胞癌患者OS和RFS的预后因素。

Objective The objectives of this study were to investigate the relationship between DKK1 protein expression and lymph node invasion, and prognosis in patients with intrahepatic cholangiocarcinoma. Methods From January 2005 to December 2012,78 patients with intrahepatic cholangiocarcinoma were treated with endoscopic resection. Tissue microarray of intrahepatic cholangiocarcinoma and adjacent tissues were done and biochemical indexes were measured before operation. The patients were recruited every 3 months after opera-tion. The Kaplan - Meier method was used to analyze the recurrence - free survival curve and the overall survival curve. The Cox proportional hazards regression model was used to analyze the multivariate analysis and to deter-mine the factors that affect the disease - free survival （RFS） and overall survival （ OS） . Results There were sig-nificant differences in the expression of GGT, hepatic portal lymph node invasion, Child - Pugh grade, MMP9 and DKK1 protein in the negative and positive expression of intrahepatic cholangiocarcinoma（ P 〈0. 05） . The positive expression rate of DKK1 protein in intrahepatic cholangiocarcinoma was 35. 90% （28/78） , and the positive ex-pression rate of DKK1 protein in hilar cholangiocarcinoma was 14. 10% （11/78） . RFS and OS in 78 cases of in-trahepatic cholangiocarcinoma were 51.28% （40/78 ） and 50. 00% （38/78） ,41.03% （32/78） and 38. 46% （30/ 78） ,25. 64% （20/78） and 23. 08% （ 18/78） after surgery for 1,3 and 5 years,respectively. The results from uni-variate and multivariate analysis showed that GGT,CA19 -9,CEA,tumor size,DKKl and hilar lymph node inva-sion were the prognostic factors of OS in patients with intrahepatic cholangiocarcinoma. CEA, tumor size, DKK1 and hilar lymph node involvement were prognostic factors for RFS in patients with intrahepatic cholangiocarcino- ma. DKK1 protein expression positive and negative OS curve or RFS curve showed that 5 years after intrahepatic cholangiocarcinoma patients DKK1 protein expression positive and negative OS were 28. 20% and 20. 51 % ; RFS were 24. 36% and 21.79% . Conclusion The expression of DKK1 protein is closely related to lymph node inva-sion in patients with intrahepatic cholangiocarcinoma. The expression of DKK1 protein is the prognostic factor of OS and RFS in patients with intrahepatic cholangiocarcinoma.