HBx和HIF-1α在肝癌血管生成中的关系及临床意义

Correlation of hepatitis B virus X protein and hypoxia-inducible factor-1α expression with angiogenesis and metastasis in HBV related hepatocellular carcinoma

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。

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 HBV-related 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-1α expression was 69.35%（43/62）in HBx positive expression,significantly higher than that in HBx-negative hepatic carcinoma tissues（40.91%,9/22）and non-HBV related hepatic carcinoma tissues（36.36%,8/22）.HIF-1α expression showed no statistical difference between HBx-negative hepatic carcinoma tissues and non-HBV related hepatic carcinoma tissues.HBx expression was positively correlated with HIF-1α 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 carcinoma tissues than that in both HBx-negative hepatic carcinoma tissues and non-HBV related hepatic carcinoma 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.