HBx和HIF-1α在肝癌血管生成中的关系及临床意义

摘要

Objective To investigate the roles of HBx and HIF-1α expression in angiogenesis and metastasis of HBV related hepatocellular carcinoma. Methods Immunohistochemistry was used to detect the expression of HBx, HIF-1α and CD34 in 84 cases of HBVrelated hepatic carcinoma and 22 cases of non-HBV related hepatic carcinoma. Results The positive rate of HBx was 73. 81％( 62/84 )in HBV-related hepatocellular carcinoma tissues. The positive rate of HIF-Ia expression was 69. 35％( 43/62 )in HBx positive expression, significantly higher than that in HBx-negative hepatic carcinoma tissues( 40. 9l％ ,9/22 )and non-HBV related hepatic carcinoma tissues( 36. 36％ , 8/22 ). HIF-1α expression showed no statistical difference hetween HBx-negative hepatic carcinoma tissues and non-HBV related hepatic carcinoma tissues. HBx expression was positively correlated with HIF-Ia expression( rs = 0. 573 ,P ＜0. 01 ).The expression of both HBx and HIF-1α in well differentiated tissues was higher than that in the poor( P <0.05 ).and it was also higher in metastasis tissues than that in non-metastasis tissues. MVD was significantly higher in HBx-positive hepatic c:arcinoma tissues than that in both HBx-negative hepatic carcinoma tissues and non-HBV related hepatic carcmoma tissues( P ＜ 0. 01 ). MVD in cases of metastasis was higher than that of non-metastasis( P＜0. 01 ) , and also higher in cases of portal vein invasion than that of non-invasion( P ＜0. 05 ). Conclusion HBx and HIF-1α are widely expressed in HBV related hepatocellular carcinoma tissues , and show a significantly positive relationship. HBx may play an important role in angiogenesis of hepatocellular carcinoma by upregulating HIF-1α expression.%目的 探讨乙肝病毒X蛋白(hepatitis B virus X protein,HBx)与缺氧诱导因子-1α(hypoxia-inducible factor,HIF-1α)在乙肝相关性肝细胞肝癌(hepatocellular carcinoma,HCC)组织血管生成及转移中的作用.方法 选择84例乙肝相关性肝癌组织和22例非乙肝相关性肝癌组织,免疫组化法检测HBx、HIF-1α及血管内皮细胞表面抗原(CD34)表达,光镜下记录微血管计数(microvessel density,MVD).结果 84例乙肝相关性肝癌组织中HBx阳性表达率为73.81%(62/84).62例HBx阳性表达组中的HIF-1α阳性率为69.35%(43/62),明显高于HBx阴性组40.91%(9/22)和非乙肝相关性肝癌组36.36%(8/22)(P<0.05).HBx阴性表达的乙肝相关性肝癌组和非乙肝相关性肝癌组中HIF-1α阳性表达无统计学意义(P>0.05).HBx和HIF-1α的表达呈正相关(rs=0.573,P<0.01);HBx和HIF-1α在高分化肿瘤组织中的表达高于低分化组织(P<0.05),且转移组表达高于无转移组;HBx阳性表达组平均MVD值明显高于HBx阴性组和非乙肝相关性肝癌组(P<0.01),有转移组MVD高于无转移组(P<0.01);有门脉侵犯组高于非侵犯组(P<0.05).结论 HBx和HIF-1α广泛表达于乙肝相关性肝癌组织中,二者呈正相关;HBx可能通过上调HIF-1α的表达在乙肝相关性肝癌组织血管生成及转移中起促进作用.