摘要
目的基于生物信息学分析EphB4在肝细胞癌(hepatocellular carcinoma,HCC)中的表达及作用,进一步探讨EphB4在HCC血管生成中的作用。方法收集UALCAN数据库中EphB4在HCC中的研究信息,并分析EphB4的表达水平与HCC患者临床病理指标相关性。利用Genecards数据库分析EphB4蛋白富集的功能以及相关的蛋白,并应用String构建EphB4共表达蛋白网络图,DAVID对EphB4共表达蛋白网络进行功能富集和KEGG分析。进一步通过免疫组化验证EphB4在HCC组织中的表达,并分析EphB4与HCC组织内皮细胞标志物(CD31)和HCC组织微血管密度(microvascular density,MVD)的关系。结果EphB4在HCC组织中明显高表达(P<0.05),HCC中异常高表达的EphB4与HCC的病理分期相关(P<0.05)。通过Genecards分析,发现EphB4的功能主要富集血管的萌芽和新生、细胞发育和迁移、轴突的引导、蛋白的磷酸化等。通过String数据库发现10个与EphB4密切相关的蛋白,进一步通过DAVID数据库对EphB4共表达蛋白进行GO分析,发现功能主要富集在细胞的运动、血管的萌芽和生成、信号通路的激活、细胞骨架形成、T细胞的调节等;参与的通路为轴突传递、Ras系统、Ephrin信号系统、VEGF信号通路、PI3K-AKT信号通路等。免疫组化结果表明EphB4在HCC中高表达,EphB4表达水平与CD31的表达水平呈正相关(R=0.85,P<0.0001);EphB4高表达的HCC组织中MVD计数明显增加(P<0.0001)。结论EphB4在HCC组织中高表达,并参与调节HCC组织的血管生成。
Objective To analyze the expression and role of EphB4 in hepatocellular carcinoma(HCC)based on bioinformatics,and to further explore the role of EphB4 in angiogenesis of HCC.Methods The research of EphB4 in HCC in the UALCAN database was collected,and the correlation between the expression level of EphB4 and the clinicopathological indicators of HCC patients was analyzed.The Genecards database was used to analyze the functions of EphB4,and String was used to construct the EphB4 co-expressed protein network diagram.DAVID was used to perform functional enrichment and KEGG analysis of the EphB4 co-expressed protein network.The expression of EphB4 in HCC tissues was further verified by immunohistochemistry,and the relationship between EphB4 and HCC tissue endothelial cell marker(CD31)and HCC tissue microvascular density(MVD)was analyzed.Results EphB4 was significantly expressed in HCC tissues(P<0.05).The abnormally high expression of EphB4 in HCC was associated with the pathological stage of HCC(P<0.05).Genecards analysis showed that EphB4 mainly enriched in the sprouting and regeneration of blood vessels,cell development and migration,axon guidance,and protein phosphorylation.Ten proteins closely related to EphB4 were found through String database,and GO analysis of EphB4 co-expressed proteins was further conducted through DAVID database.It was found that the functions were mainly enriched in cell movement,blood vessel sprouting and generation,activation of signaling pathways,and cytoskeleton formation,regulation of T cells,etc.The pathways involved were axonal transmission,Ras system,Ephrin signaling system,VEGF signaling pathway,PI3K-AKT signaling pathway,etc.Immunohistochemical results showed that EphB4 was highly expressed in HCC,and the expression level of EphB4 was positively correlated with the expression level of CD31(R=0.85,P<0.0001).MVD count was significantly increased in HCC tissues with high EphB4 expression(P<0.0001).Conclusion EphB4 is highly ex-pressed in HCC tissues and participates in the regulation of angiogenesis in HCC.
作者
张秋令
施金枝
朱纪玲
戴锴
佘莎
ZHANG Qiuling;SHI Jinzhi;ZHU Jiling;DAI Kai;SHE Sha(Department of Infectious Diseases,Renmin Hospital of Wuhan University,Wuhan 430060,China)
出处
《胃肠病学和肝病学杂志》
2025年第2期189-194,共6页
Chinese Journal of Gastroenterology and Hepatology
基金
国家自然科学基金(81972673)
武汉大学人民医院交叉创新人才项目(JCRCFZ-2022-028)。
