基于TCGA研究左右半结肠癌基因表达差异及苦参-大血藤-半枝莲作用机制  

Study on the Difference of Gene Expression Between Left and Right Colon Cancer and the Mechanism of Sophorae Flavescentis Radix-Sargentodoxae Caulis-Scutellariae Barbatae Herba Based on TCGA

作　　者：刘菁菁 张恩欣 LIU Jing-Jing;ZHANG En-Xin(The First Clinical Medical School of Guangzhou University of Chinese Medicine,Guangzhou 510405 Guangdong,China;Shenzhen Bao’an Pure Chinese Medicine Treatment Hospital,Shenzhen 518100 Guangdong,China)

机构地区：[1]广州中医药大学第一临床医学院,广东广州510405 [2]深圳市宝安纯中医治疗医院,广东深圳518100

出　　处：《广州中医药大学学报》2024年第3期742-751,共10页Journal of Guangzhou University of Traditional Chinese Medicine

基　　金：广东省自然科学基金面上项目(编号:2021A1515011232)。

摘　　要：【目的】探讨左半结肠癌与右半结肠癌的基因表达差异及大肠癌核心药对苦参-大血藤-半枝莲作用于左右半结肠癌的机制差异。【方法】下载134例左半结肠癌及194例右半结肠癌患者癌症基因组图谱(TCGA)的转录组数据,应用R软件实现2组差异基因分析及京都基因与基因组百科全书(KEGG)通路富集分析;通过BATMAN-TCM数据库获取苦参-大血藤-半枝莲药对的活性成分及靶点,基于左右半结肠癌差异基因,分别进行药对-左/右半结肠癌KEGG富集分析、蛋白质互作(PPI)网络构建,比较药对治疗左、右半结肠癌富集的生物信号通路差异及关键靶点差异。【结果】左半结肠癌与右半结肠癌相对于正常癌旁组织共同的差异表达基因共6051个,左半结肠癌特异性的差异表达基因共1958个,右半结肠癌特异性的差异表达基因共1739个;左半结肠癌特异性KEGG富集通路14条,右半结肠癌特异性KEGG富集通路23条。苦参-大血藤-半枝莲药对活性化合物共85个,对应的靶点合计469个,药对-左半结肠癌靶点富集于10条KEGG信号通路,关键靶点为DRD2、CACNA1C、HTR3A、COMT、TH,药对-右半结肠癌靶点富集于1条KEGG信号通路,核心靶点为HTR3A、DRD2、TH、AGT、GRIN2B。【结论】左半结肠癌与右半结肠癌存在基因表达差异:左半结肠癌与免疫功能异常、AMPK信号通路异常等机制有关,右半结肠癌与中性粒细胞外陷阱形成、酒精中毒、Hippo信号通路异常等机制有关。除调控细胞周期及必需氨基酸代谢等机制外,苦参-大血藤-半枝莲药对对调节左半结肠癌肠道内分泌功能、抑制右半结肠癌炎症反应具有特异性作用,亦可能对结肠癌患者具有情绪调控作用。Objective To investigate the gene expression differences between left-sided colon cancer and right-sided colon cancer and the mechanism differences between the colorectal cancer core drug pairs of Sophorae Flavescentis Radix-Sargentodoxae Caulis-Scutellariae Barbatae Herba acting on left-sided and right-sided colon cancer.Methods The transcriptome data of 134 patients with left-sided colon cancer and 194 patients with right-sided colon cancer from The Cancer Genome Atlas(TCGA)were downloaded,and the R software was applied to realize the differential gene analysis of the two groups and the enrichment analysis of Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway;the BATMAN-TCM database was used to obtain the active ingredients and targets of the drug pair of Sophorae Flavescentis Radix-Sargentodoxae Caulis-Scutellariae Barbatae Herba,and based on the different genes of the left-and right-sided colon cancers,KEGG enrichment analysis of the drug pair-left/right-sided colon cancers was performed respectively,and the protein-protein-interaction(PPI)network was constructed to compare the differences of the biosignaling pathways enriched by the drug pairs for the treatment of left-and right-sided colon cancers,as well as the differences of the key target points.Results There were 6051 differentially expressed genes common to left-and right-sided colon cancers relative to normal paracancerous tissues,1958differentially expressed genes specific to left-sidedcolon cancer,and 1739 differentially expressed genes specific to right-sided colon cancer;14 KEGG-enriched pathways specific to left-sided colon cancer,and 23 KEGG-enriched pathways specific to right-sided colon cancer.There were 85 active compounds in the drug-pair of Sophorae Flavescentis Radix-Sargentodoxae Caulis-Scutellariae Barbatae Herba,corresponding to a total of 469 targets.The drug-pair-left-sided colon cancer targets were enriched in 10 KEGG signaling pathways,with the key targets being DRD2,CACNA1C,HTR3A,COMT,and TH;and the drug-pair-rightsided colon can

关 键 词：苦参 大血藤 半枝莲 左半结肠癌 右半结肠癌 差异基因 情绪调控 癌基因组图谱(TCGA) 

分 类 号：R285.5[医药卫生—中药学]