解整合素-金属蛋白酶10及肝细胞配体B2在乙肝-肝纤维化-肝癌患者中的表达  

Expression and potential clinical applications of ADAM10 and Ephrin-B2 in patients with HBV-related hepatic fibrosis and hepatocellular carcinoma of different stages

作　　者：李凤 李恒力 张宪峰 李宁 台剑熊 鲍鸿斌 LI Feng;LI Heng-li;ZHANG Xian-feng;LI Ning;TAI Jian-xiong;BAO Hong-bin(Department of Hepatobiliary and Pancreatic Surgery,Hengshui People′s Hospital,Hengshui 053000,Hebei,China)

机构地区：[1]衡水市人民医院肝胆胰外科,河北衡水053000

出　　处：《广东医学》2024年第4期485-493,共9页Guangdong Medical Journal

基　　金：河北省医学科学研究课题计划(20200401)。

摘　　要：目的探讨解整合素-金属蛋白酶10(ADAM10)、肝细胞配体B2(Ephrin-B2)在“肝炎-肝纤维化-肝癌”轴中的表达以及二者与肝纤维化之间的相关性。方法选取400例HBV感染患者为研究对象,以病情的严重程度分为肝纤维化组(200例)、肝细胞癌组(200例),将肝纤维化组进一步分为以下4个亚组:乙型肝炎组(56例)、轻度纤维化组(87例)、中度纤维化组(34例)、肝硬化组(23例),另外选取200例健康体检患者为健康对照组,对比组间血清ADAM10、Ephrin-B2、肝功能指标、肝纤维化指标;免疫组化检测健康肝组织、乙肝不同分级肝纤维化肝组织、肝癌组织间ADAM10与Ephrin-B2表达。采用t检验进行单因素分析,二元logistic进行多因素分析,皮尔逊相关性检测相关性,受试者工作特征(ROC)曲线进行诊断价值分析。结果ADAM10、Ephrin-B2、天冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)、凝血酶原时间(PT)、白蛋白(ALB)、层粘连蛋白(LN)、Ⅳ型胶原(Ⅳ-C)、透明质酸(HA)、Ⅲ型前胶原(PC-Ⅲ)水平在乙型肝炎组、轻度肝纤维化组、中度肝纤维化组、肝硬化、肝细胞癌组依次升高,且均显著高于健康对照组(P<0.05),免疫组化检测显示ADAM10、Ephrin-B2二者阳性表达在乙肝肝纤维化组织与肝癌组织中显著高于健康肝组织,且随着乙肝肝纤维化的进展Ephrin-B2、ADAM10表达显著升高。ADAM10高表达组和Ephrin-B2高表达组AST、ALT、PT、ALB、LN、Ⅳ-C、HA、PC-Ⅲ显著高于ADAM10低表达组和Ephri-B2低表达组(P<0.05)。患者血清ADAM10与Ephrin-B2呈显著正相关(P<0.05),ADAM10、Ephrin-B与血清AST、ALT、PT、ALB、LN、Ⅳ-C、HA、PC-Ⅲ以及肝纤维化分期呈显著正相关(P<0.05)。ADAM10、Ephrin-B2、AST、ALT、PT、ALB、LN、Ⅳ-C、HA、PC-Ⅲ为HBV感染患者患“肝炎-肝纤维化-肝癌”轴进展的影响因素。ADAM10诊断肝纤维化、肝细胞癌曲线下面积(AUC)分别为0.680、0.713,敏感度为0.821、0Objective To investigate the expression of a disintegrin and metalloproteinase 10(ADAM10)and Ephrin-B2 in the Hepatitis-Hepatic Fibrosis-Hepatocellular Carcinoma axis,and investigate their correlation with hepatic fibrosis severity.Methods A total of 400 HBV-infected patients were categorized into the hepatic fibrosis group(200 cases)and the hepatocellular carcinoma group(200 cases)based on disease severity.The hepatic fibrosis group was further divided into four subgroups:hepatitis B group(56 cases),mild fibrosis group(87 cases),moderate fibrosis group(34 cases),and cirrhosis group(23 cases).Additionally,200 healthy individuals were selected as the control group.Serum levels of ADAM10,Ephrin-B2,liver function indicators,and fibrosis markers were compared among the groups.Immunohistochemistry was performed to assess the expression of ADAM10 and Ephrin-B2 in healthy liver tissues,different stages of HBV-related hepatic fibrosis tissues,and HCC tissues.Single-factor analysis was conducted using t-tests,multivariate analysis using binary logistic regression,Pearson correlation analysis for correlations,and ROC curve analysis for diagnostic value.Results Levels of ADAM10,Ephrin-B2,aspartate aminotransferase(AST),alanine aminotransferase(ALT),prothrombin time(PT),albumin(ALB),laminin(LN),typeⅣcollagen(Ⅳ-C),hyaluronic acid(HA),and typeⅢprocollagen(PC-Ⅲ)increased sequentially in the hepatitis B group,mild fibrosis group,moderate fibrosis group,cirrhosis group,and hepatocellular carcinoma group,and were significantly higher than those in the healthy control group(P<0.05).Immunohistochemistry revealed that the positive expression of ADAM10 and Ephrin-B2 in HBV-related hepatic fibrosis tissues and HCC tissues was significantly higher than in healthy liver tissues.With the progression of HBV-related hepatic fibrosis,the expression of Ephrin-B2 and ADAM10 significantly increased.Patients with high expression of ADAM10 and Ephrin-B2 had significantly higher levels of AST,ALT,PT,ALB,LN,Ⅳ-C,HA,and PC-Ⅲthan those wit

关 键 词：乙肝 肝纤维化 肝癌 解整合素-金属蛋白酶10 肝细胞配体B2 

分 类 号：R735.7[医药卫生—肿瘤] R575.2[医药卫生—临床医学]