基于m^(6)A相关lncRNA的女性肺腺癌预后风险模型  

A prognostic risk model for female lung adenocarcinomas based on m^(6)A-related lncRNAs

作　　者：王梦梦 夏祥伟[1] 胡滨滨 Wang Mengmeng;Xia Xiangwei;Hu Binbin(Cancer Institute,Gaoyou People′s Hospital,Gaoyou 225600,China)

机构地区：[1]高邮市人民医院肿瘤中心,高邮225600

出　　处：《国际呼吸杂志》2024年第5期519-528,共10页International Journal of Respiration

基　　金：2022年度高邮市卫生健康委员会医学科研立项项目(GY20221203)。

摘　　要：目的建立m^(6)A相关长链非编码RNA(lncRNA)女性肺腺癌患者的预后风险模型,并分析有代表性的m^(6)A相关lncRNA在女性肺腺癌患者治疗和预后中的作用。方法从TCGA数据库下载女性肺腺癌患者的RNA表达数据(291例肿瘤组织和34例正常组织)和临床数据(280例)。采用limma包分析23个m^(6)A甲基化修饰基因的表达情况。根据TCGA上关于基因集合ID的说明,检索并收集女性肺腺癌lncRNA表达的数据。从GENCODE下载m^(6)A调节基因的转录组学数据。采用共表达相关性分析筛选m^(6)A相关lncRNA。采用limma包对筛选的m^(6)A相关lncRNA进行差异分析。采用survival、Cox回归分析包进行Kaplan-Meier、单因素和多因素Cox回归分析、受试者操作特征曲线[曲线下面积(AUC)>0.65]分析,进一步筛选预后lncRNA。选取AUC最大的lncRNA(AP001981.2)作为代表性的m^(6)A相关lncRNA,用于确认预测特征。采用rms包,通过将AP001981.2表达水平与年龄和临床分期相结合建立列线图。采用校准曲线检验预测与现实之间的一致性。按照AP001981.2的logFC进行分组,logFC>0为高表达组(131例),logFC<0为低表达组(131例)。采用oncoPredict包进行2组患者的药物敏感性分析。通过enrichplot包行基因集富集分析,探讨AP001981.2的参与通路。结果23个m^(6)A调节器分子中有15个基因差异表达,其中有6个基因表达下调,9个基因表达上调。共识别了16876个lncRNA,并鉴定出了2910个m^(6)A相关lncRNA,其中有1156个差异表达m^(6)A相关lncRNA。经Kaplan-Meier、单因素Cox回归分析筛选,共有17个与女性肺腺癌患者预后相关的lncRNA。多因素Cox分析显示有10个lncRNA可作为独立预后因子,其中9个lncRNA可作为独立危险因子(AL157931.1、AL359853.1、AC007128.1、AC005618.1、LINC01138、AC103591.4、AP001981.2、AC243772.2和AC078983.1),1个lncRNA可作为独立保护因子(AC018529.1)。选择AUC最大(0.736)的AP001981.2作为代表性的m^(6)A相关lncRNA。�Objective To establish a prognostic risk model for female lung adenocarcinomas based on m^(6)A-related long non-coding RNAs(lncRNAs),and to analyze the therapeutic and prognostic potentials of representative m^(6)A-related lncRNAs in female lung adenocarcinoma patients.Methods A dataset containing RNA expressions of 291 female lung adenocarcinoma specimens and 34 normal tissues as well as clinical data of 280 female lung adenocarcinoma patients was downloaded from The Cancer Genome Atlas(TCGA)database database.Using limma package in R,expressions of 23 genes with m^(6)A methylation modification were analyzed.LncRNA expressions in female lung adenocarcinoma specimens were collected based on the description of gene set IDs on TCGA.Transcriptomic data of m^(6)A regulatory genes were downloaded from GENCODE.Co-expression correlation analysis was performed to screen m^(6)A-related lncRNAs in female lung adenocarcinomas,and their differential expressions were analyzed using the limma package.Kaplan-Meier,univariate and multivariate Cox regression analysis,and receiver operating characteristic(ROC)curve(area under the curve[AUC]>0.65)analysis were performed using survival and Cox regression packages in R to further screen prognostic m^(6)A-related lncRNA in female lung adenocarcinomas.LncRNA AP001981.2 with the largest AUC was selected as the representative m^(6)A-related lncRNA in female adenocarcinomas and subjected to the validation of the prognostic potential.Using the RMS package,a nomogram was established by combining the representative m^(6)A-related lncRNA with age and tumor staging of female lung adenocarcinomas.Calibration curves were plotted to verify the consistency between predictions and actual conditions.According to the log fold change(FC)of lncRNA AP001981.2,female lung adenocarcinoma patients were divided into high-level group(logFC>0,n=131)and low-level group(logFC<0,n=131).Using oncoPredict package,drug sensitivity analysis was performed.Using the enrichplot package,the gene set enrichment analysis(G

关 键 词：肺腺癌 RNA 长链非编码 女性 AP001981.2 m^(6)A 

分 类 号：R734.2[医药卫生—肿瘤]