乙酰肝素酶和低氧诱导因子1α在胆管癌中的表达及其临床意义

Expression of heparanase and hypoxia-inducible factor-1α in cholangiocarcinoma

目的检测乙酰肝素酶(heparanase)和低氧诱导因子1α(HIF-1α)在胆管癌中的表达,分析其与预后的关系并探讨HIF-1α对调节heparanase的可能机制。方法用免疫组化方法检测48例胆管癌组织中heparanase、HIF-1α蛋白的表达,并分析其与临床病理因素以及预后之间的关系。结果 Heparanase和HIF-1α在48例胆管癌中的阳性表达率分别为62.5%和45.9%,显著高于癌旁组织。Heparanase阳性表达与TNM分期(P=0.031)、淋巴结转移(P=0.003)呈正相关,与3年生存率呈负相关(20.0%vs.0%,P=0.001);HIF-1α与淋巴结转移(P=0.017)、远处转移(P=0.031)正相关,与预后无相关。Heparanase与HIF-1α有较高的共同阳性表达率(P=0.018)。多因素分析显示heparanase和HIF-1α均为非影响预后的独立因素。结论 Heparanase在胆管癌中表达增高且与预后不良相关,HIF-1α可能上调heparanase表达水平,促进heparanase介导的肿瘤浸润转移。

Objective To detect the expressions of heparanase and hypoxia-inducible factor-1α（HIF-1α） in cholangiocarcinoma and analyze their relationship with prognosis and explore the possible mechanism of HIF-1α for regulation of heparanase.Methods Heparanase and HIF-1α proteins in the tumor and adjacent tissues were detected by immunohistochemistry in 48 patients with cholangiocarcinoma and analyzed their relationship with clinicopathological significance and prognosis.Results Heparanase and HIF-1α proteins were found in 30（62.5%） and 22（45.9%） tumor specimens,respectively,significantly higher than that in the adjacent tissues.High heparanase expression was closely correlated to advanced TNM stage（P=0.031）,lymph node metastasis（P=0.003） and negatively correlated to 3-year postoperative survival（20.0% vs.0%,P=0.001）.HIF-1α expression was associated with lymph node metastasis（P=0.017） and distant metastasis（P=0.031）,but had a higher positive rate in heparanase-positive cases than in heparanase-negative cases（P=0.018）.Multivariate analysis showed that neither heparanase nor HIF-1α was the independent prognostic factor.Conclusion Heparanase is overexpressed in cholangiocarcinoma in association with decreased postoperative survival.HIF-1α may up-regulate heparanase expression and promote heparanase-mediated tumor invasion and metastasis.