慢性日本血吸虫病肝纤维化差异表达基因的生物信息学分析  

Bioinformatics analysis of differentially expressed genes associated with chronic schistosomiasis japonica-induced hepatic fibrosis

作　　者：杜志祥[1] 李阳[2] 王子健 周大明[2] 杨江华[1] DU Zhi-xiang;LI Yang;WANG Zi-jian;ZHOU Da-ming;YANG Jiang-hua(Department of Infectious Diseases,Yijishan Hospital of Wannan Medical College,Wuhu,Anhui 241001,China;Department of Infectious Diseases,People’s Hospital of Taizhou City,Jiangsu Province,China)

机构地区：[1]皖南医学院弋矶山医院感染性疾病科,安徽芜湖241001 [2]江苏省泰州市人民医院感染性疾病科

出　　处：《中国血吸虫病防治杂志》2022年第4期352-360,369,共10页Chinese Journal of Schistosomiasis Control

基　　金：国家自然科学基金青年基金(30700694)。

摘　　要：目的筛选慢性日本血吸虫病肝纤维化差异表达基因(differentially expressed genes,DEGs),并对其功能进行分析。方法从基因表达综合(Gene Expression Omnibus,GEO)数据库下载慢性日本血吸虫病肝纤维化患者测序表达谱数据集,利用R语言进行DEGs筛选,对其生物学功能进行基因本体论(Gene Ontology,GO)和京都基因和基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)富集分析并构建蛋白质-蛋白质相互作用(protein-protein interaction,PPI)网络,以筛选关键基因。结果共鉴定出62个DEGs,其中12个下调表达基因、50个上调表达基因。GO富集分析显示,DEGs主要富集在脂肪酸、硫化合物、酰基辅酶A、硫酯代谢等116种生物学过程,线粒体基质、线粒体外膜、细胞器外膜等19种细胞组分及胰岛素样生长因子结合、氧化还原酶活性等7种分子功能。KEGG通路富集分析显示,DEGs与磷脂酰肌醇-3-激酶/丝苏氨酸蛋白激酶(phosphatidylinositol-3-kinase/serine/threonine protein kinase,PI3K/Akt)、丝裂原活化蛋白激酶(mitogen-activated protein kinase,MAPK)信号通路、钙离子代谢以及环磷酸腺苷(cyclic adenosine monophosphate,cAMP)信号传导等功能密切相关。PPI网络分析发现ACACA、ACSL1、GPAM、THRSP、PLIN1、DGAT2等6个与慢性日本血吸虫病肝纤维化发生有关的关键基因,其中核心程度居前3位的基因是ACSL1、ACACA和PLIN1。结论ACSL1、ACACA和PLIN1可能是导致慢性日本血吸虫病肝纤维化发生的关键基因,其调控的脂质代谢异常可能在慢性日本血吸虫病患者肝纤维化进程中发挥了重要作用。Objective To screen differentially expressed genes(DEGs)associated with chronic schistosomiasis japonica-induced hepatic fibrosis and analyze their functions.Methods schistosomiasis japonica-induced hepatic fibrosis was downloaded from the Gene Expression Omnibus(GEO)database,and DEGs were screened using R package.The biological functions of DEGs were characterized using Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses.In addition,the protein-protein interaction(PPI)network of DEGs was created to screen the hub genes.ResultsA total of 62 DEGs were identified,including 12 down-regulated genes and 50 up-regulated genes.GO enrichment analysis showed that DEGs were mainly enriched in 116 biological processes,including fatty acid,sulfur compound,acyl-coenzyme A and thioester metabolism;19 cellular components,including mitochondrial matrix,outer mitochondrial membrane and organelle outer membrane;and 7 molecular functions,including insulin-like growth factor binding and oxidoreductase activity.KEGG pathway enrichment analysis that the DEGs were significantly enriched in phosphatidylinositol-3-kinase/serine/threonine protein kinase(PI3K/Akt),mitogen-activated protein kinase(MAPK),calcium metabolism and cyclic adenosine monophosphate(cAMP)signaling.PPI network analysis identified six hub genes involved in the development of chronic schistosomiasis japonica-induced hepatic fibrosis,including ACACA,ACSL1,GPAM,THRSP,PLIN1 and DGAT2,and ACSL1,ACACA and PLIN1 were the top 3 hub genes.Conclusions ACSL1,ACACA and PLIN1 may be the hub genes associated with the development of chronic schistosomiasis japonica-induced hepatic fibrosis,and abnormal lipid metabolism mediated by these DEGs may play an important role in the development of chronic schistosomiasis japonica-induced hepatic fibrosis.

关 键 词：慢性日本血吸虫病 肝纤维化 差异表达基因 生物信息学分析 

分 类 号：R532.21[医药卫生—内科学]