基因富集分析HER2基因对胃癌免疫微环境的影响

An Analysis of the Effect of HER2 Gene on the Immune Microenvironment of Gastric Cancer by Gene Enrichment Analysis

目的:运用基因富集分析探索HER2基因表达状态对胃癌生物学功能和代谢通路的影响,并进一步探讨其对胃癌免疫微环境的影响。方法:下载癌症基因组图谱(TCGA)数据库的胃癌转录组数据,根据HER2 mRNA表达水平分为高低表达组、应用R语言和GSEA软件进行富集分析。结果:GO富集分析表明,HER2基因高低表达组的差异基因主要参与骨化、细胞外基质组织、胶原纤维组织、结缔组织发育等过程;KEGG分析富集的信号通路主要为PI3K-AKT信号通路、黏着斑信号通路、刺激神经组织的配体–受体互作通路;GSEA软件分析HER2高表达组mTOR信号通路、Notch信号通路、磷酸戊糖途径信号通路、神经营养素信号通路等表达上调。结论:细胞外基质状态、PI3K-AKT信号通路、黏着斑信号通路、mTOR信号通路、Notch信号通路可能与HER2阳性胃癌侵袭性强、免疫治疗明显获益相关。

Objective: To investigate the effect of HER2 gene expression on the biological function and metabol-ic pathways of gastric cancer by gene enrichment analysis, and further explore its effect on the im-mune microenvironment of gastric cancer. Methods: The transcriptome data of gastric cancer from The Cancer Genome Atlas (TCGA) database were downloaded and divided into high and low expres-sion groups according to the expression level of HER2 mRNA. Enrichment analysis was performed using R language and GSEA software. Results: GO enrichment analysis showed that the differentially expressed HER2 genes in high and low expression groups were mainly involved in ossification, and development of extracellular matrix tissue, collagen fiber tissue and connective tissue. KEGG analy-sis showed that the enriched signaling pathways were mainly PI3K-AKT signaling pathway, adhe-sion plaque signaling pathway and ligand-receptor interaction pathway that stimulated nerve tis-sue. GSEA software analysis showed that the expression of aminoacyl tRNA signaling pathway, mTOR signaling pathway, Notch signaling pathway, pentose phosphate signaling pathway and neu-rotrophic signaling pathway in HER2 high expression group was up-regulated. Conclusion: The ex-tracellular matrix status, PI3K-AKT signaling pathway, adhesion plaque signaling pathway, mTOR signaling pathway, Notch signaling pathway may be associated with strong invasiveness and signif-icant efficacy of immunotherapy in HER2-positive gastric cancer.