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

LI Feng; LI Heng-li; ZHANG Xian-feng; LI Ning; TAI Jian-xiong; BAO Hong-bin

doi:10.13820/j.cnki.gdyx.20233011

Abstract：Objective 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 he-patic 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 tis-sues,different stages of HBV-related hepatic fibrosis tissues,and HCC tissues.Single-factor analysis was conducted u-sing t-tests,multivariate analysis using binary logistic regression,Pearson correlation analysis for correlations,and ROC curve analysis for diagnostic value.Results Levels of ADAM 10,Ephrin-B2,aspartate aminotransferase(AST),ala-nine aminotransferase(ALT),prothrombin time(PT),albumin(ALB),laminin(LN),type Ⅳ collagen(Ⅳ-C),hyaluronic acid(HA),and type Ⅲ procollagen(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 tis-sues.With the progression of HBV-related hepatic fibrosis,the expression of Ephrin-B2 and ADAM10 significantly in-creased.Patients with high expression of ADAM10 and Ephrin-B2 had significantly higher levels of AST,ALT,PT,ALB,LN,Ⅳ-C,HA,and PC-Ⅲ than those with low expression(P＜0.05).Serum ADAM10 and Ephrin-B2 lev-els were significantly positively correlated(P＜0.05),and both were significantly correlated with serum AST,ALT,PT,ALB,LN,Ⅳ-C,HA,PC-Ⅲ,and hepatic fibrosis stage(P＜0.05).ADAM10,Ephrin-B2,AST,ALT,PT,ALB,LN,Ⅳ-C,HA,and PC-Ⅲ were identified as influencing factors in the progression of the Hepatitis-Hepatic Fibrosis-Hepatocellular Carcinoma axis in HBV-infected patients.The diagnostic AUC of ADAM10 for hepatic fibrosis and hepatocellular carcinoma were 0.680 and 0.713,with sensitivity of 0.821 and 0.794,and specificity of 0.577 and 0.639,respectively.The diagnostic AUC of Ephrin-B2 for hepatic fibrosis and hepatocellular carcinoma were 0.663 and 0.730,with sensitivity of 0.757 and 0.834,and specificity of 0.651 and 0.693,respectively.Conclusion ADAM10 and Ephrin-B2 exhibit an increasing expression trend in the progression of the"Hepatitis-Hepatic Fibrosis-Hepatocel-lular Carcinoma"axis.They may play crucial roles in the occurrence and development of hepatic fibrosis and hepatocellu-lar carcinoma in HBV-infected patients.ADAM10 and Ephrin-B2 have the potential to become important serum mark-ers for diagnosing and monitoring the diseases in the Hepatitis-Hepatic Fibrosis-Hepatocellular Carcinoma axis.