作者
Zhixiang Du,Y Li,Z J Wang,Da Ming Zhou,Jianghua Yang
摘要
To screen differentially expressed genes (DEGs) associated with chronic schistosomiasis japonica-induced hepatic fibrosis and analyze their functions.The dataset of gene expression profiles of patients with chronic 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.A 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.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.[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。.