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中国癌症防治杂志

中国癌症防治杂志 ›› 2019, Vol. 11 ›› Issue (6): 454-460.doi: 10.3969/j.issn.1674-5671.2019.06.02

• 肿瘤生物信息学专栏 • 上一篇    下一篇

基于生物信息学方法探讨Her-2基因表达对胃癌免疫细胞浸润的影响

  

  1. 解放军总医院第一医学中心肿瘤内科
  • 出版日期:2019-12-25 发布日期:2020-01-19
  • 通讯作者: 胡毅 E-mail：huyi0401@aliyun.com
  • 基金资助:
    国家重点专项精准医学项目（2017YFC0907904）

Exploring the effect of Her-2 gene expression on immune cell infiltration in gastric cancer based on bioinformatics method

  • Online:2019-12-25 Published:2020-01-19

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摘要： 目的 探讨人类表皮生长因子受体2（human epidermal growth factor receptor-2，Her-2）对胃癌组织中免疫细胞浸润的影响及可能的机制。方法 从癌症基因组图谱（the Cancer Genome Atlas，TCGA）数据库下载胃癌转录测序数据及临床资料。采用CIBERSORT反卷积算法获得胃癌微环境中浸润的免疫细胞占比，分析其与Her-2表达的关系，筛选Her-2基因潜在的调控浸润免疫细胞的类型。采用基因集变异分析（gene set variation analysis，GSVA）评估与胃癌组织Her-2表达相关的信号通路集合，利用GEO（gene expression omnibus）收录的胃癌转录组数据验证Her-2基因表达与胃癌免疫细胞浸润程度的关系。结果 CIBERSORT分析TCGA数据库胃癌样本发现CD8+T细胞、静息状态记忆性CD4+T细胞、M0型巨噬细胞及肥大细胞在Her-2高表达及低表达组中的浸润程度差异有统计学意义（P=0.029，0.049，0.027，0.008）。GEO数据库与TCGA数据库分析结果均显示，Her-2基因高表达与CD8+ T细胞、静息状态记忆性CD4+T细胞、M0型巨噬细胞及肥大细胞的发育、诱导分化、迁移调控有关（P<0.05），并影响胃癌组织中部分免疫细胞的浸润能力和程度。结论 在胃癌中Her-2基因高表达可能对部分免疫细胞形成和功能发挥具有抑制作用。

关键词: 胃癌, 人类表皮生长因子受体2, 肿瘤免疫细胞浸润, 分子机制, 生物信息学

Abstract: Objective To explore the effect of human epidermal growth factor receptor-2 （Her-2） on immune cell infiltration in gastric cancer tissues and its possible mechanism. Methods The RNA-Seq data of 354 patients with complete information were downloaded from the TCGA. The CIBERSORT algorithm was used to investigate the proportion of infiltrating immune cells in the microenvironment of gastric cancer，and its correlation with Her-2 expression was analyzed to screen the potential types of Her-2 genes regulating infiltrating immune cells. Gene set variation analysis（GSVA） was used to evaluate the set of signal pathways related to Her-2 expression in gastric cancer tissues，and gastric transcriptome data collected by Gene Expression Omnibus（GEO） was used to further verify the relationship between Her-2 gene expression and the degree of gastric cancer immune cell infiltration. Results CIBERSORT analysis of gastric cancer samples from the TCGA database found that CD8+ T cells，resting memory CD4+ T cells，M0 macrophages，and mast cells infiltrated differentially in Her-2 high- and low-expression groups（P=0.029，0.049，0.027，0.008）. High expression of Her-2 gene was related to the development，induction，differentiation，and migration regulation of CD8+ T cells，resting memory CD4+ T cells，M0 macrophages and mast cells（P<0.05），and affected the infiltration capacity and proportion of some immune cells in gastric cancer tissues. Conclusion High expression of Her-2 gene in gastric cancer may have an inhibitory effect on the formation and function of some immune cells.

Key words: Gastric cancer, Her-2, Tumor immune cells infiltration, Molecular mechanism, Bioinformatics

中图分类号: 

  • R735.2