黄芪抗肿瘤相关靶基因筛选、生物学功能分析及关键基因水平与非小细胞肺癌和乳腺癌预后的关系

Screening of anti-tumor related target genes of Astragalus membranaceus,analysis of their biological function,and the relationships between expression of key genes and prognosis of non-small-cell lung cancer and breast cancer

目的筛选中药黄芪抗肿瘤相关靶基因,分析黄芪抗肿瘤相关靶基因生物学功能,探讨黄芪抗肿瘤相关靶基因中的关键基因表达水平与非小细胞肺癌和乳腺癌预后的关系。方法在中医大百科全书数据库(ETCM)中对中药黄芪进行检索,筛选黄芪抗肿瘤相关靶基因。采用基因本体论(GO)分析黄芪抗肿瘤相关靶基因生物学功能,京都基因和基因组百科全书(KEGG)分析黄芪抗肿瘤相关靶基因信号通路。采用STRING数据库构建上述基因编码蛋白相互作用网络(PPI),分析网络中蛋白相互作用关系,并采用Cytoscape软件筛选网络中的关键基因,对关键基因表达水平与非小细胞肺癌和乳腺癌预后关系进行分析。结果黄芪抗肿瘤相关靶基因有TVAII、TOP2A、SHMT1、POLR2A、POLR2D等,其生物学功能主要富集于谷氨酰胺代谢、嘌呤化合物合成、己糖转运等;相关基因细胞成分主要富集于氧谷氨酸脱氢酶复合物、过氧化物酶体和线粒体膜等;分子功能主要富集于氧化还原酶活性、羧基裂解酶活性和糖代谢等。KEGG信号通路主要富集于维甲酸信号通路、TP53调节代谢基因信号通路及叶酸代谢信号通路等。黄芪抗肿瘤关键基因为POLR2A、POLR2D、POLR2G。POLR2D基因表达水平与非小细胞肺癌(HR=1.20,P=0.04)及乳腺癌(HR=1.40,P=0.04)存在正相关性。结论黄芪抗肿瘤相关靶基因有TVAII、TOP2A、SHMT1、POLR2A、POLR2D等,其生物学功能主要与谷氨酰胺代谢等有关、细胞成分主要富集于氧谷氨酸脱氢酶复合物等、分子功能主要参与氧化还原酶活性等。KEGG信号通路主要富集于维甲酸信号通路等。黄芪抗肿瘤关键基因POLR2D高表达的非小细胞肺癌、乳腺癌患者生存期短。

Objective To screen out the antitumor related target genes of Astragalus membranaceus and analyze their biological function,and to investigate the relationship between the expression of key genes of the antitumor related target genes of Astragalus membranaceus and the prognosis of patients with nonsmallcell lung cancer(NSCLC)or breast cancer.Methods The Encyclopedia of Traditional Chinese Medicine(ETCM)database was used to screen out the antitumor related target genes of Astragalus membranaceus.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(Kyoto Encyclopedia)were used to analyze the biological functions and related signaling pathways of antitumor target genes of Astragalus membranaceus.Proteinprotein interaction network(PPI)was constructed by using STRING database.The proteinprotein interaction relationship in the network was analyzed.The key genes in the network were screened out by Cytoscape software,and the relationships between the expression levels of key genes and the prognosis of NSCLC or breast cancer were analyzed.Results The target genes of Astragalus membranaceus were TVAII,TOP2A,SHMT1,POLR2A,POLR2D,etc.Their biological functions were mainly enriched in glutamine metabolism,purine compound synthesis,hexose transport,etc.The cell components of the related genes were mainly enriched in the glutamate dehydrogencomplex,peroxisome enzyme and mitochondrial membrane,etc.The molecular functions were mainly enriched in the oxidoreductase activity,carboxyl cleavage,enzyme activity,and sugar metabolism.KEGG signaling pathway was mainly enriched in the retinoic acid signaling pathway,TP53 regulatory gene signaling pathway,and folate metabolism signaling pathway.The key antitumor bases of Astragalus membranaceus were POLR2A,POLR2D and POLR2G.The POLR2D gene expression was positively correlated with NSCLC(HR=1.20,P=0.04)and breast cancer(HR=1.40,P=0.04).Conclusions Astragalus membranaceus may play an antitumor role through POLR2A,POLR2D and POLR2G genes.The high expression of POLR2D is related to the short survival time of patients with NSCLC and breast cancer,which is expected to become a prognostic molecular marker of NSCLC and breast cancer.