HMGB1在肝细胞癌中的表达及其与VEGF、MVD的关系

Correlations of HMGB1 expression with VEGF and microvascular density in hepatocellular carcinoma

摘要:

目的：探讨高迁移率族蛋白1(High mobility group protein box-1，HMGB1)在肝细胞癌组织中的表达及其与血管内皮生长因子（Vascular endothelial growth factor，VEGF）表达、肿瘤微血管密度（Microvascular density，MVD）的关系和临床意义。方法：免疫组织化学SP法检测HMGB1、VEGF和CD34在37例人肝癌组织及相应癌旁肝组织和10例人正常肝组织中的表达；并用抗CD34抗体标记微血管，计数微血管密度；应用Western blot技术定量检测HMGB1在10例肝癌及相应癌旁和5例正常肝组织的表达情况。结果：HMGB1蛋白在肝癌组织中的表达明显高于癌旁组织及正常肝组织。HMGB1的表达与肿瘤大小、门静脉侵犯相关（P=0.018；P=0.036）。肝癌组织中HMGB1表达与VEGF表达及MVD间均呈正相关(r=0.544，P=0.001；r=0.672，P＜0.05)。结论：肝癌组织中异常表达增高的HMGB1、VEGF与肝癌微血管生成过程相关，HMGB1可能成为阻断肝癌血管生成的有效靶点。

Abstract:

Objective:To investigate the correlations of high mobility group protein box-1 (HMGB1) expression with vascular endothelial growth factor (VEGF) expression and microvessel density (MVD) in hepatocellular carcinoma (HCC) and its clinical significance. Methods:Expressions of HMGB1, VEGF and CD34 were detected with immunohistochemistry in 37 specimens of HCC tissues and the corresponding adjacent tumor tissues, and 10 cases of normal hepatic tissues. The MVD was calculated using CD34 antibody as an endothelial marker. Western blot was performed in 10 HCC tissues and the corresponding adjacent tumor tissues, and 5 normal hepatic tissues. Results:Expression of HMGB1 appeared at a high level compared to adjacent tumor tissues and normal hepatic tissues. HMGB1 expression was significantly correlated with the tumor size and the portal venous invasion. HMGB1 expression was positively correlated with VEGF expression and MVD in HCC（r=0.544, P=0.001；r=0.672，P＜0.05）. Conclusion:Upregulation of HMGB1 and VEGF are involved in the angiogenesis of HCC, and HMGB1 may be a therapeutic target for angiogenesis in HCC.