基于TCGA数据库的扶正消积进展方抑制结直肠癌肝转移机制网络药理学研究  

Network pharmacological study on the mechanism of Fuzheng Xiaoji Jinzhan Fang(扶正消积进展方)inhibiting liver metastasis of colorectal cancer based on TCGA database

作　　者：李琼 陈敬贤[1] 武渊 吕玲玲[1] 应海峰[1] 朱文华 徐佳悦 阮铭[1] 郭元彪[1] 朱伟荣 殷世鹏[2] 郑岚[1] LI Qiong;CHEN Jingxian;WU Yuan;LYU Lingling;YING Haifeng;ZHU Wenhua;XU Jiayue;RUAN Ming;GUO Yuanbiao;ZHU Weirong;YIN Shipeng;ZHENG Lan(Department of Traditional Chinese Medicine,Ruijin Hospital Affiliated to Shanghai Jiao Tong University,Shanghai,200000,China;Library of Gansu University of Chinese Medicine,Lanzhou,Gansu,730101,China)

机构地区：[1]上海交通大学医学院附属瑞金医院中医科,上海200000 [2]甘肃中医药大学图书馆,甘肃兰州730101

出　　处：《甘肃中医药大学学报》2023年第3期1-11,共11页Journal of Gansu University of Chinese Medicine

基　　金：国家自然科学基金青年项目(82104749);上海市青年科技英才扬帆计划资助项目(21YF1426000);上海市中医药事业发展三年行动计划项目(2018-2020FWTX-1101);上海市卫生健康委员会中医药科研项目(2020lz007)。

摘　　要：目的基于癌症基因组图谱计划(TCGA)数据库,采用网络药理学的方法探究扶正消积进展方抑制结直肠癌肝转移的作用机制,为扶正消积进展方进一步的临床应用及转化提供依据。方法采用中药系统药理学数据库与分析平台(TCMSP)和中草药数据库(TCMID)筛选药物的有效成分,采用BATMAN数据库预测有效成分的目标靶点,利用TCGA数据库及R语言Mfuzz包预测、筛选结直肠癌肝转移的疾病靶点,药物有效成分的目标靶点与疾病靶点相交获得交集靶点;对交集靶点进行基因本体(GO)功能富集分析与京都基因与基因组百科全书(KEGG)通路富集分析;通过STRING10.0数据库、Cytoscape3.7.2软件对交集靶点进行蛋白质-蛋白质相互作用(PPI)网络构建,进而筛选出核心靶点;采用Cytoscape3.7.2的“Merge”功能构建“药物-有效成分-靶点-作用通路”网络图。结果共筛选获得扶正消积进展方有效成分282个,交集靶标152个;涉及13类生物功能,139个分子功能,80个细胞功能;通过PPI网络发掘出OXTR、GNA15、F2、COX5A、COX5B、ATP5B、COX4I1、COX7C、COX7B、ATP5A1等10个核心靶点,KEGG信号通路主要富集在多种神经退行性变的途径、神经活性配体受体相互作用、钙信号通路等方面。结论扶正消积进展方可通过多种有效成分,多途径、多靶点抑制结直肠癌肝转移。Objective Based on The Cancer Genome Atlas(TCGA)database,to explore the mechanism of the inhibitory effect of Fuzheng Xiaoji Jinzhan Fang(扶正消积进展方)on liver metastasis of colorectal cancer using network pharmacology methods,to provide a basis for further clinical application and transformation of Fuzheng Xiaoji Jinzhan Fang.Methods TCMSP and TCMID were used to screen the active ingredients of drugs,BATMAN database was used to predict the target points of active ingredients,and TCGA database and R Mfuzzy package were used to predict and screen the disease targets of colorectal cancer liver metastasis;Gene Ontology(GO)function enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were carried out for intersection targets;construct a protein-protein interaction(PPI)network for intersecting targets using STRING10.0 database and Cytoscape3.7.2 software,and then screen out core targets;construct a“drug-active ingredient-target-action pathway”network diagram using the“Merge”function of Cytoscape3.7.2.Results A total of 282 effective ingredients were selected from the Fuzheng Xiaoji Jinzhan Fang;152 intersecting targets,involving 13 types of biological functions,139 molecular functions,and 80 cellular functions.Through the PPI network,10 core targets were discovered,including OXTR,GNA15,F2,COX5A,COX5B,ATP5B,COX4I1,COX7C,COX7B,and ATP5A1.The KEGG signaling pathway is mainly enriched in various pathways of neurodegeneration,neural active ligand receptor interactions,and calcium signaling pathways.Conclusion Fuzheng Xiaoji Jinzhan Fang can inhibit liver metastasis of colon cancer through multiple effective ingredients,pathways,and targets.

关 键 词：扶正消积进展方 结直肠癌肝转移 网络药理学 癌症基因组图谱计划数据库 有效成分 核心靶点 信号通路 

分 类 号：R285[医药卫生—中药学] R735.3[医药卫生—中医学]