【摘要】 目的:筛选出肺腺癌(LUAD)的预后相关因子,并分析LUAD中免疫细胞浸润情况。方法:从癌症基因组图谱(TCGA)数据库中下载LUAD转录组RNA——Seq数据集,应用反卷积算法(CIBERSORT)和估计算法(ESTIMATE)计算患者肿瘤浸润性免疫细胞(TIC)的比例以及免疫和基质成分的数量。利用R软件鉴定LUAD患者与正常人的差异表达基因(DEGs),并进行功能和通路富集分析。采用单变量Cox回归分析和蛋白质-蛋白质相互作用(PPI)网络构建方法对DEGs交叉分析,确定LUAD预后相关因子,并选择其中一个预后因子进行单基因分析,最后利用CIBERSORT分析LUAD中免疫细胞浸润情况。结果:共鉴定出363个DEGs,对DEGs进行Cox回归分析和PPI网络构建后,交叉分析得到7个预后相关基因,分别为CCR2、CD79A、BTK、CD19、CD22、CD28、PTPRC。选定CD22进行单基因分析,发现CD22的表达与LUAD患者的临床病理特征(临床分期、肿瘤浸润)呈负相关,与LUAD患者的生存期呈正相关。基因集富集分析(GSEA)显示,免疫相关活性基因集主要富集于CD22高表达组,而代谢途径基因集主要富集于CD22低表达组。CIBERSORT分析表明其中记忆B细胞、幼稚B细胞、静息肥大细胞、静息的CD4~+记忆T细胞、CD8~+T细胞、调节T细胞与CD22表达呈正相关,提示CD22可能对TME中的免疫优势存在起重要作用。结论:CCR2、CD79A、BTK、CD19、CD22、CD28和PTPRC表达水平可能有助于预测和解释LUAD患者预后,其中CD22还可以作为区分TME免疫活跃状态和代谢活动状态的指标,为LUAD的治疗提供新思路。免疫细胞浸润分析结果为LUAD的分子机制研究提供新思路。更多还原

【Abstract】 Objective:Screening for the prognostic factors of lung adenocarcinoma(LUAD)and analyzing the infiltration of immune cell in LUAD.Methods:The LUAD transcriptome RNA-Seq dataset was downloaded from the cancer genome map(TCGA)database. The proportion of tumor infiltrating immune cell(TIC)and the number of immune and stromal components were calculated by CIBERSORT and ESTIMATE. The differentially expressed genes(DEGs)between LUAD patients and normal controls were identified by R software,and the function and pathway enrichment analysis was performed. Then Univariate Cox regression analysis and protein-protein interaction(PPI)network construction were used to determine the prognostic factors of DEGs,and one of the prognostic factors was selected for single gene analysis. Finally,CIBERSORT was used to analyze the immune cell infiltration in LUAD.Results:A total of 363 DEGs were identified. After Cox regression analysis and PPI network construction of DEGs,seven prognostic related genes were obtained by cross analysis,which were CCR2,CD79 A,BTK,CD19,CD22,CD28 and PTPRC. CD22 was selected for single gene analysis. It was found that the expression of CD22 was negatively correlated with the clinicopathological features(clinical stage,tumor invasion)of LUAD patients,and positively correlated with the survival time of LUAD patients. Gene Set Enrichment Analysis(GSEA)showed that the immune-related active genomes were mainly concentrated in the CD22 high expression group,while the metabolic pathway genomes were mainly concentrated in the CD22 low expression group. CIBERSORT analysis showed that memory B cells,naive B cells,resting mast cells,resting CD4~+T cells,CD8~+T cells and regulatory T cells were positively correlated with CD22 expression,suggesting that CD22 may play an important role in immune dominance in TME.Conclusion:The expression levels of CCR2,CD79 A,BTK,CD19,CD22,CD28 and PTPRC may be helpful to predict and explain the prognosis of patients with LUAD.CD22 can also be used as an index to distinguish immune activity from metabolic activity in TME,which provides a new idea for the treatment of LUAD. The results of immune cell infiltration analysis provide a new idea for the study of the molecular mechanism of LUAD.更多还原