胃癌突变基因与患者预后及免疫功能的相关性  

ASSOCIATION OF MUTATION GENES WITH PROGNOSIS AND IMMUNE FUNCTION IN PATIENTS WITH GASTRIC CANCER

作　　者：曾周 龚拯 刘丽丽[1] 柯丁心 王斌[1,2] 张万明 ZENG Zhou;GONG Zheng;LIU Lili;KE Dingxin;WANG Bin;ZHANG Wanming(School of Basic Medicine,Qingdao University,Qingdao 266071,China)

机构地区：[1]青岛大学基础医学院,山东青岛266071 [2]青岛大学华赛医学细胞和蛋白质药物研究院

出　　处：《精准医学杂志》2022年第4期322-325,331,共5页Journal of Precision Medicine

基　　金：山东省重点研发计划项目(2019JZZY011009)。

摘　　要：目的通过生物信息学方法筛选和分析肿瘤数据库中胃癌突变基因,并分析其与患者预后及免疫功能的相关性,为胃癌患者的免疫治疗提供理论和数据参考。方法从TCGA及ICGC数据库中下载胃癌患者的基因突变及临床数据,通过R软件筛选出与胃癌患者生存率和预后密切相关的共同高频突变基因。并对高频突变基因进行GSEA富集分析,运用CIBERSORT算法计算肿瘤浸润免疫细胞的相对丰度,探究共同高频突变基因对肿瘤浸润免疫细胞的影响。结果在TCGA和ICGC数据库中发现21个共同的高频突变基因,其中FAT4与患者临床预后及肿瘤突变负荷相关。通过GSEA富集分析和CIBERSORT算法,发现FAT4突变与免疫系统相关信号通路的激活及免疫应答的增强相关。结论胃癌中FAT4突变频率较高,且其突变与患者较好的预后及抗肿瘤免疫功能的增强相关。因此,FAT4具有作为预测胃癌患者免疫应答的生物标记物的潜力。Objective To investigate the association of mutation genes in tumor database with the prognosis and immune function of gastric cancer patients by using bioinformatics methods,and to provide a theoretical and data reference for immunothe-rapy of gastric cancer patients.Methods Gene mutation and clinical data of gastric cancer patients were downloaded from the TCGA and ICGC databases,and R software was used to screen out the high-frequency mutation genes closely associated with both the survival rate and prognosis of gastric cancer patients.GSEA enrichment analysis was conducted for high-frequency mutation genes,and the CIBERSORT algorithm was used to calculate the relative abundance of tumor-infiltrating immune cells,so as to explore the impact of common high-frequency mutation genes on tumor-infiltrating immune cells.Results A total of 21 common high-frequency mutation genes were screened out in the TCGA and ICGC databases,among which FAT 4 was associated with clinical prognosis and tumor mutation burden.GSEA enrichment analysis and CIBERSORT algorithm showed that FAT 4 mutation was associated with the activation of immune system-related signaling pathways and the enhancement of immune response.Conclusion The FAT 4 gene has the highest frequency of mutation,and its mutation is associated with a better prognosis of patients and the enhancement of antitumor immune function.Therefore,FAT 4 has the potential of being used as a biomarker to predict immune response in patients with gastric cancer.

关 键 词：胃肿瘤 肿瘤突变负荷 突变率 钙黏着糖蛋白类 免疫疗法 生物标记 肿瘤 预后 数据库 遗传学 

分 类 号：R735.2[医药卫生—肿瘤] R319.1[医药卫生—临床医学]