摘要
目的:根据加权基因共表达网络(WGCNA)探索槲皮素抗胃癌的潜在生物靶标。方法:利用TCGA数据库下载胃癌相关转录组和临床数据,分析胃癌转录组表达的差异基因,利用网络药理学找到槲皮素的作用靶点,找出槲皮素与胃癌的hub基因。通过KEGG通路,GO基因富集分析寻找hub基因的靶点及通路,探索hub基因的在胃癌临床数据中的生存分析和性状表达的差异。结果:1)共发现槲皮素142个靶点,共139个蛋白质-蛋白质相互作用关系;2)KEGG通路富集分析发现槲皮素抗胃癌的作用通路可能与细胞衰老、MicroRNAs的表达、P53信号通路有关;3)生存分析发现纤溶酶原激活物抑制剂-1(SERPINE1)、微囊蛋白-1(Caveolin-1)、雄性激素受体(AR)、转录因子E2F2(E2F2)、前列腺素E2受体EP3亚型(PTGER3)在胃癌中的表达差异会影响患者的预后(P<0.05);4)在胃癌的TNM分期中,AR与PTGER3的表达差异与胃癌的分期相关(P<0.05);5)GEPIA数据库分析,AR与PTGER3在胃癌组织中的表达存在一定的相关性(P<0.05)。结论:槲皮素抗胃癌机制可能和细胞凋亡、MicroRNAs表达和P53信号通路有关,通过多靶点作用于SERPINE1、CAV1、AR、E2F2、PTGER3,发挥抑制癌细胞,改善患者预后的作用。
Objective:To explore the potential biological target of quercetin against gastric cancer based on the weighted gene co-expression network(WGCNA).Methods:TCGA database was used to download gastric cancer related transcriptome and clinical data to analyze the differential genes expressed in gastric cancer transcriptome.Meanwhile,network pharmacological means was used to find the drug action targets of quercetin and find the hub genes of quercetin in gastric cancer.The targets and pathways of hub genes were searched through KEGG pathway and GO gene enrichment analysis which were aimed to explore the survival analysis and trait expression differences of hub genes in clinical data of gastric cancer.Results:1)A total of 142 targets and 139 protein interactions were found for quercetin.2)Enrichment analysis of KEGG pathway found that the anti-gastric cancer pathways of quercetin may be related to cell senescence,the expression of MicroRNAs,and the P53 signaling pathway.3)Survival analysis found that the expression differences of plasminogen activator inhibitor-1(SERPINE1),microencapsulated protein-1(Caveolin-1),androgen receptor(AR),transcription factor E2F2(E2F2),and prostagtin E2 receptor EP3 subtype(PTGER3)in gastric cancer affected the prognosis of patients(P<0.05).4)In TNM staging of gastric cancer,the difference in expression of AR and PTGER3 was correlated with the staging of gastric cancer(P<0.05).5)GEPIA database analysis showed that there was a certain correlation between AR and PTGER3 expression in gastric cancer tissues(P<0.05).Conclusion:The anti-gastric cancer mechanism of quercetin may be related to apoptosis,MicroRNAs expression and P53 signaling pathway.It acts on SERPINE1,CAV1,AR,E2F2,and PTGER3 through multiple targets to inhibit cancer cells and improve the prognosis of patients.
作者
张林
欧祥琴
张涛
钟凯
吴学会
李睿思
李青璇
梁峰
张轩
ZHANG Lin;OU Xiangqin;ZHANG Tao;ZHONG Kai;WU Xuehui;LI Ruisi;LI Qingxuan;LIANG Feng;ZHANG Xuan(First Teaching Hospital of Tianjin University of Traditional Chinese Medicine,Tianjin 300193,China;The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine,Guiyang 550001,China;Tianjin University of Traditional Chinese Medicine,Tianjin 301608,China;School of Chinese Medicine,Hong Kong Baptist University,Hong Kong 99077,China)
出处
《世界中医药》
CAS
2021年第4期546-552,共7页
World Chinese Medicine
基金
国家自然科学基金项目(81704198)——基于数据挖掘与运气学说的香港地区气象疫病监测预警系统研究。
关键词
加权基因共表达网络
胃癌
hub基因
槲皮素
Weighted gene co-expression network
Gastric cancer
Hub genes
Quercetin
