摘要
目的通过生物信息学方法分析与胃癌发病密切相关的基因调控网络,探讨其在胃癌预后中的价值,并进一步挖掘靶向治疗胃癌的中药活性成分。方法通过GEO数据库获取GSE103236胃癌芯片数据,对芯片数据进行均一化处理,分析胃癌组织与正常胃组织的差异表达基因(differentially expressed genes,DEGs);应用Metascape数据库对DEGs进行基因本体论(genetic ontology,GO)和京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)通路分析;通过String数据库构建DEGs蛋白交互作用网络;采用Cytohubba筛选关键基因,分析关键基因表达程度与患者的预后及免疫细胞浸润的相关性;运用CTD数据库筛选能靶向作用于关键DEGs的中药活性成分。结果共获得45015个胃癌组织与正常组织的DEGs,其中显著性DEGs 176个。它们与细胞周期过程调控、丝裂原活化蛋白激酶(mitogen activated protein kinases,MAPK)级联调控等生物过程密切相关,集中于细胞外区域、细胞外泌体等细胞组分,主要参与胰岛素样生长因子结合、Wnt蛋白结合等细胞功能。KEGG分析发现显著性DEGs主要参与环磷酸酰胺(cyclic adenosine monophosphate,cAMP)信号通路、磷脂酰肌醇3-激酶/蛋白激酶B(phosphatidylinositide 3-kinases/protein kinase B,PI3K/Akt)信号通路、癌症转录失调、p53信号级联等信号通路。筛选出TIMP1、SPP1、APOE、APOB、FGA、FGG、CYR61、IGFBP1、CHGB、SCG310个关键基因。这些基因表达异常均与免疫细胞的大范围浸润存在极高的相关性,其中TIMP1、IGFBP1、CYR61、FGG、APOE、APOB 6个关键基因的异常表达显著影响患者的生存率。进一步挖掘出桦木酸、长春新碱、丹参酮等30个可能靶向治疗胃癌的中药活性成分。结论筛选出10个与胃癌发病密切相关的核心基因,并分析了这些核心基因与胃癌患者预后及免疫细胞浸润的相关性;挖掘出30个可能用于胃癌靶向治疗的中药活性�
Objective To analyze the gene regulatory network closely related to gastric cancer through bioinformatics methods,explore its value in the prognosis of gastric cancer,and further explore the active ingredients of traditional Chinese medicine for targeted therapy of gastric cancer.Methods GSE103236 gastric cancer chip data was obtained from the GEO database,and the chip data was homogenized to analyze the differentially expressed genes(DEGs)between gastric cancer tissue and normal gastric tissue.The genetic ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG)pathways were analyzed on DEGs using the Metascape database,and DEGs protein interaction network was constructed through String database.The key genes were screened by Cytohubba,and the correlation between the expression of key genes and prognosis and infiltration of immune cells was analyzed.CTD database was used to screen active components of traditional Chinese medicine which could target the key genes.Results A total of 45015 DEGs from gastric cancer and normal tissue were obtained,of which 176 were significant DEGs.These significant DEGs were closely related to cell cycle process regulation,mitogen activated protein kinases(MAPK)cascade regulation and other biological processes.They were concentrated in the extracellular werea,cellular exosomes and other cellular components,and were mainly involved in cell functions such as insulin-like growth factor binding and Wnt protein binding.The KEGG analysis found that DEGs were mainly involved in cyclic adenosine monophosphate(cAMP)signaling pathway,phosphatidylinositide 3-kinases/protein kinase B(PI3K/Akt)signaling pathway,cancer transcription disorder,p53 signaling cascade and other signaling pathways.Ten hub genes:TIMP1,SPP1,APOE,APOB,FGA,FGG,CYR61,IGFBP1,CHGB,SCG3 were screened out.The abnormal expression of these genes were highly correlated with the large-scale infiltration of immune cells.Among them,the abnormal expression of the six key genes of TIMP1,IGFBP1,CYR61,FGG,APOE,and APOB could signific
作者
宋厚盼
刘恒铭
仇婧玥
冯瑶
吴嫚婷
喻昶
熊萌
曾梅艳
SONG Hou-pan;LIU Heng-ming;QIU Jing-yue;FENG Yao;WU Man-ting;YU Chang;XIONG Meng;ZENG Mei-yan(Hunan Provincial Key Laboratory of Diagnostic Research in Chinese Medicine,Hunan University of Chinese Medicine,Changsha 410208,China;Faculty of Medicine,Hunan University of Chinese Medicine,Changsha 410208,China;Key Laboratory of TCM Heart and Lung Syndrome Differentiation&Medicated Diet and Dietotherapy,Hunan University of Chinese Medicine,Changsha 410208,China)
出处
《中草药》
CAS
CSCD
北大核心
2021年第22期6939-6952,共14页
Chinese Traditional and Herbal Drugs
基金
国家自然科学基金青年科学基金项目(81703920)
湖湘青年科技创新人才项目(2021RC3101)
湖南省自然科学基金青年科学基金项目(2019JJ50442)
湖南中医药大学校级科研基金项目(2020XJJJ012)
湖南省教育厅科研一般项目(19C1426)。
关键词
胃癌
差异表达基因
生物信息学
中药活性成分
免疫细胞浸润
预后分析
桦木酸
长春新碱
丹参酮
gastric cancer
differentially expressed genes
bioinformatics
active components of traditional Chinese medicine
immune cell infiltration
prognosis analysis
betulinic acid
vincristine
tanshinone
