肺腺癌焦亡相关特征模型的构建和验证  

Construction and validation of a model for pyroptosis-related features in lung adenocarcinoma

作　　者：王杨淑怡 叶威 林志豪 黄约诺 方涛 董晓亭 WANG Yangshuyi;YE WEI;LIN Zhihao;HUANG Yuenuo;FANG Tao;DONG Xiaoting(Zhejiang University of Traditional Chinese Medicine,Wenzhou 325000,Zhejiang,China)

机构地区：[1]浙江中医药大学附属温州中医院,浙江温州325000

出　　处：《检验医学》2023年第9期833-841,共9页Laboratory Medicine

基　　金：温州市科技计划项目(2021Y0839)。

摘　　要：目的基于生物信息学方法构建肺腺癌(LUAD)-细胞焦亡基因预后风险模型,探讨LUAD与细胞焦亡的关系。方法从肿瘤基因组图谱(TCGA)数据库下载LUAD患者的转录组数据(TCGA队列)和临床资料,采用limma程序包鉴别差异表达的焦亡基因。根据差异焦亡基因的表达特征对TCGA队列进行聚类分析,以获得聚类分型,鉴定不同聚类分型间的差异表达基因。采用LASSO-Cox回归分析建立基于不同聚类分型差异表达基因的预后风险模型,并计算风险评分。依据风险评分的中位值将TCGA队列的LUAD患者分为高风险组、低风险组。结合临床病理特征,采用Kaplan-Meier生存曲线和Cox回归分析探讨预后风险模型的临床价值。根据TCGA队列的风险评分中位值将从基因表达综合(GEO)数据库中筛选出的LUAD患者分为高风险组和低风险组,对预后风险模型进行验证。对TCGA队列高、低风险组差异表达基因进行基因本体论(GO)和京都基因与基因组数据库(KEGG)富集分析。采用单样本基因集富集分析(ssGSEA)和CIBERSORT程序包对TCGA队列的免疫细胞和免疫相关通路进行量化和比较。结果在LUAD癌组织和癌旁组织中鉴定出41个差异表达的焦亡基因。聚类分析结果显示,TCGA队列样本可分为2个聚类分型,分型2的生存期显著长于分型1(P<0.05)。鉴定出11个与LUAD患者生存相关的差异表达基因(ANO1、PKHD1L1、FMO2、TDRD1、TBX4、ABCC12、AQP4、CPXM2、WFIKKN2、ATP1A4、IGSF10)。Kaplan-Meier生存曲线分析结果显示,TCGA队列高风险组生存期显著短于低风险组(P<0.05)。采用GEO队列进行验证,得出了相同的结果。Cox回归分析结果显示,依据预后风险模型得出的风险评分是LUAD患者预后的独立危险因素。基于TCGA队列11个差异表达基因的热图分析结果显示,高风险组、低风险组之间性别、临床分期、T分期、N分期差异均有统计学意义(P<0.05)。TCGA队列高风险组和低�Objective To construct a prognostic model of lung adenocarcinoma(LUAD)-pyroptosis genes based on bioinformatics,and to investigate the relationship between LUAD and cell pyroptosis.Methods The transcriptomic data of LUAD patients(TCGA cohort)and clinical data were downloaded from the Cancer Genome Atlas(TCGA),and the limma program package was used to identify differentially expressed pyroptosis genes.Cluster typing was obtained from TCGA cohort based on the expression characteristics of differentially expressed pyroptosis genes,and differentially expressed pyroptosis genes between clustering were identified.Using least absolute shrinkage and selection operator(LASSO)-Cox regression method,a prognostic model based on interclustering differentially expressed pyroptosis genes was developed,and the risk scores were calculated.TCGA cohort LUAD patients were classified into high and low risk groups using the median risk score.The clinical prognostic role of the prognostic model was analyzed using Kaplan-Meier survival curve and Cox regression analysis in conjunction with clinical characteristics.The LUAD patients from the Gene Expression Omnibus(GEO)were classified into 2 risk groups(high and low)using the median risk score of the TCGA cohort,and the clinical prognostic validation was performed.The signaling pathways and biological functions of differentially expressed pyroptosis genes in TCGA cohort were analyzed using Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis.Single sample gene set enrichment analysis(ssGSEA)and CIBERSORT were used to compare immune cells and immune-related pathways.Results Totally,41 differentially expressed pyroptosis genes were identified in LUAD tissues and paracancer tissues.The results of cluster analysis showed that TCGA cohort samples could be classified into 2 cluster types,and the survival time of type 2 was longer than that of type 1(P<0.05).Totally,11 differentially expressed pyroptosis genes(ANO1,PKHD1L1,FMO2,TDRD1,TBX4,ABCC12,AQP4,CPXM2,WFIKKN2,ATP1A4 an

关 键 词：细胞焦亡基因 肺腺癌 肿瘤基因组图谱数据库 预后 免疫浸润细胞 

分 类 号：R393[医药卫生—基础医学]