肿瘤突变负荷与免疫细胞浸润联合分析在非小细胞肺癌预后评估中的意义  

Clinical Significance of Tumor Mutation Burden and Immune Cell Infiltration Analysis in Prognosis Evaluation of Non-small Cell Lung Cancer

作　　者：谢琛[1] 许晨 陈淑慧 李俊玉[1] 张怀文[1] XIE Chen;XU Chen;CHEN Shuhui(Jiangxi Cancer Hospital,Nanchang,330029)

机构地区：[1]江西省肿瘤医院,330029

出　　处：《实用癌症杂志》2023年第12期1956-1962,1967,共8页The Practical Journal of Cancer

基　　金：江西省卫生健康委科技计划项目(编号:20201089);江西省肿瘤医院科研开放基金项目(编号:2021J15)。

摘　　要：目的探讨肿瘤突变负荷(TMB)在评估非小细胞肺癌(NSCLC)免疫治疗预后中的价值以及TMB与免疫浸润之间的关系。方法从TCGA数据库中分别下载肺腺癌(LUAD)及肺鳞癌(LUSC)患者体细胞基因突变数据、转录组数据及临床数据。根据突变数据计算TMB评分,并根据训练计算出最佳TMB阈值,将患者分为低TMB和高TMB组。分析低TMB组和高TMB组之间差异表达基因(DEGs)、免疫细胞浸润和生存情况。通过GEPIA在线数据库查询了肺癌组织中的基因表达。结果从TCGA获得了641例肺腺癌(LUAD)和506例肺鳞癌(LUSC)患者的样本信息,高、低TMB组的生存分析结果表明,高TMB组患者的生存率优于低TMB组患者。研究中共鉴定了756个DEGs,基因集富集分析(GSEA)显示,低TMB组的DEGs富集于免疫相关途径。在获得的差异表达基因中,借助ImmPort数据库筛选出15个免疫相关的关键基因,包括5个预后相关基因(CD274、PDCD1、CTLA4、LAG3、TIGIT)。PDCD1、CTLA4、LAG3、TIGIT在肺癌组织中的表达无差异,CD274在肺癌组织中的表达有差异。免疫浸润分析发现CD8+T细胞、激活期记忆CD4+T细胞、M1巨噬细胞在高TMB组中浸润高于低TMB组,同时CXCL17高表达是TMB与免疫浸润预后好的独立基因。结论高TMB的LUAD患者的生存率优于低TMB的LUAD患者,可能与CD8+T细胞、激活期记忆CD4+T细胞、M1巨噬细胞免疫浸润及CXCL17高表达有关。Objective To investigate the prognosis role of TMB in the NSCLC patients and the relationship between TMB and immune infiltration.Methods Somatic gene mutation,transcriptome data and clinical data of NSCLC patients were collected from TCGA database.According to tumor mutation burden data,we got TMB score.Then we divided patients into high-TMB group and low-TMB group according to the average TMB score.Differentially expressed genes(DEGs),immune cell in?ltration and survival analysis were compared between the low-TMB and high-TMB groups.We queried the expression of genes in lung cancer tissues through the GEPIA online database and performed experimental validation of the function of aberrant genes expressed in lung cancer tissues.Results We got 641 LUAD and 506 LUSC patients from TCGA database and the results of survival analysis for the high-and low-TMB groups suggested that patients in the low-TMB group had poor survival rates than those in the high-TMB group.A total of 756 DEGs were identi?ed in the study,and gene set enrichment analysis(GSEA)showed that DEGs in the low-TMB group were enriched in immune-related pathways.Among the differentially expressed genes obtained,15 immune-related key genes were screened with the help of ImmPort database,including 5 prognosis-related genes(CD274,PDCD1,CTLA4,LAG3,TIGIT).No difference in the expression of PDCD1,CTLA4,LAG3,TIGIT in lung cancer tissues and differential expression of CD274 in lung cancer tissues.Immune infiltration analysis revealed that CD8+T cells,activation-phase memory CD4+T cells,and M1 macrophages were infiltrated higher in the high TMB group than in the low TMB group,while high CXCL17 expression was an independent gene for good prognosis of TMB and immune infiltration.Conclusions Survival of LUAD patien-ts with high TMB is better than that of LUAD patients with low TMB,which may be related to the immune infiltration of CD8+T cells,activation-phase memory CD4+T cells,M1 macrophages,and high expression of CXCL17.

关 键 词：肺腺癌 TCGA数据库 肿瘤突变负荷 免疫细胞浸润 预后 

分 类 号：R734.2[医药卫生—肿瘤]