基于生物信息学途径探究载脂蛋白H在肝衰竭中的功能及作用机制

Identification of Function and Mechanism of Apolipoprotein H Gene in Liver Failure Based on Bioinformatics Analysis

[目的]通过生物信息学方法,分析在肝衰竭中高表达的载脂蛋白H(APOH)在疾病发生发展中的功能与机制.[方法]从GEO数据库下载多个芯片数据集(GSE14688、GSE38941和GSE96851),以P<0.05及|log2FC|>5筛选出差异表达基因,通过Cytoscape及R对前10位关键基因中的APOH基因进行GO生物学功能富集分析和KEGG信号通路分析,并进一步在慢乙肝相关肝衰竭组织中进行表达验证.[结果]共筛选出2438个差异表达基因,其中,1162个上调基因,1276个下调基因.蛋白质相互作用网络分析发现10个枢纽基因分别为:KNG1、IGF1、SPARC、APOH、CLU、SERPING1、TGFB2、CDC37L1、PCYOX1L和APOOL.通过慢乙肝相关肝衰竭组织验证发现APOH在肝衰竭组织中高表达,GeneMANIA预测APOH和炎症反应有关.GO分析及KEGG分析显示,APOH与补体/凝血级联通路以及碳代谢通路密切相关,并且,与补体C3(complement C3)的表达水平呈明显的正相关性.[结论]APOH在肝衰竭组织中高表达,可能通过补体C3调控补体/凝血级联通路以及碳代谢通路参与肝衰竭的发生发展.

【Objective】To explore the function and mechanism of differentially expressed Apolipoprotein H(APOH)gene in liver failure by bioinformatics.【Methods】Multiple chip datasets(GSE14688,GSE38941 and GSE96851)were downloaded from the Gene Expression Omnibus(CEO)database.The differentially expressed genes were screened out based on P value<0.05 and|log2FC|>5.Biological function enrichment and KEGG pathway analysis of APOH gene,which was among the top ten key genes screened,was analyzed by Cytoscape and R,for further validation of expression of APOH in chronic hepatitis B virus-related liver failure.【Results】A total of 2438 differentially expressed genes were screened,among which 1162 were significantly up-regulated and 1276 were significantly down-regulated.According to Protein-protein Interaction Network(PPIN)analysis,the top ten key genes were KNG1,IGF1,SPARC,APOH,CLU,SERPING1,TGFB2,CDC37L1,PCYOX1L and APOOL.High expression of APOH was found in chronic hepatitis B virus-related liver failure tissues and GeneMANIA predicted that APOH was associated with inflammation.GO analysis and KEGG analysis showed that APOH,which was closely related to complement/coagulation cascade pathway and carbon metabolism pathway,positively correlated with C3(complement C3).【Conclusion】APOH is involved in the occurrence and development of liver failure by C3 regulating complement/coagulation cascade pathway and carbon metabolism pathway.