[关键词]
[摘要]
目的 探究肝癌患者的差异基因表达量与预后的相关性,以及差异基因在多种癌症的调控作用,并寻找潜在的治疗靶点以及对应中药,为临床中药的使用、中医药组方及加减用药提供依据。方法 从TCGA数据库下载肿瘤患者的转录组数据以及相应临床数据,使用R语言的edgeR包分析得出差异表达基因,并筛选、分析关键基因在泛癌的表达量及共表达情况;进一步筛选得到核心基因,研究其在泛癌中具体肿瘤的表达情况,以及肝癌临床相关性分析,并将核心基因提交至TIMER、THPA数据库,研究免疫细胞相关性和病理学情况;最后通过Coremine数据库查找核心基因对应中药,使用TCMSP、BATMAN-TCM数据库查找中药有效成分,利用Cytoscape软件制作药物-核心基因网络图,并进行京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)通路富集分析。结果 共筛选出10个关键基因,选取其中5个核心基因CCNB1、TOP2A、CCNA2、CDK1、CDC20,进行后续分析得出其与肝癌的预后生存呈负相关,与肝癌的免疫细胞呈正相关,并得到基因过表达病理学图片。其对应中药为丹参、枳实、枳壳、人参叶、人参芦、甘草、人参、蜂蜜。KEGG富集分析显示中药除调控核心基因外仍通过多靶点起作用。结论 通过生物信息学技术分析得到肝癌核心基因及相关信号通路与治疗靶点,并得到调控中药名称及其有效成分。为治疗肝癌以及其他癌症的中药复方研发提供思路。
[Key word]
[Abstract]
Objective To explore the correlation between differential gene expression in patients with liver cancer and prognosis, as well as the regulatory role of differential genes in various cancers, and find potential therapeutic targets and corresponding traditional Chinese medicine (TCM), so as to provide basis for the clinical use of TCM, the formulation of TCM and its the addition or reduction use. Methods The transcriptome data and corresponding clinical data of cancer patients in TCGA database were downloaded, and the edgeR package of R language was used to analyze the differential genes. The expression and co-expression of key genes in pan-cancer were screened and analyzed, and the core genes were further screened. The expression of the core genes in specific tumors and the clinical correlation analysis of liver cancer were studied. The core genes were submitted to TIMER and THPA databases to study the correlation of immune cells and pathology. Finally, the core corresponding TCMs were found through the Coremine database. TCMSP and BATMAN-TCM databases were used to find the effective components of TCM. Cytoscape software was used to produce drug-core gene network diagram, and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis was performed. Results A total of 10 key genes were screened, and five of them were selected as the core genes, namely CCNB1, TOP2A, CCNA2, CDK1 and CDC20. Subsequent analysis showed that they were negatively correlated with the prognosis and survival of liver cancer, and positively correlated with the immune cells of liver cancer, and the pathological pictures of gene overexpression were obtained. The core genes corresponding TCM were Danshen (Salviae Miltiorrhizae Radix et Rhizoma), Zhishi (Aurantii Fructus Immaturus), Zhike (Aurantii Fructus), Renshenye (Ginseng Folium), Renshenlu (rhizome of Panax ginseng), Gancao (Glycyrrhizae Radix et Rhizoma), Renshen (Ginseng Radix et Rhizoma), Fengmi (Mel). The KEGG enrichment analysis pathway map showed that TCM still acts through multiple targets in addition to regulating core genes. Conclusion The core genes of liver cancer and related signaling pathways and therapeutic targets obtained by bioinformatics analysis, the names of traditional Chinese medicine and their active components were obtained. To provide ideas for the treatment of liver cancer and other cancers.
[中图分类号]
R285
[基金项目]
国家中医临床研究基地业务建设项目第二批科研专项(JDZX2015183)