基于TCGA数据库分析三阴性乳腺癌预后与铁死亡相关lncRNA的关系

Analysis of relationship between prognosis and ferroptosis-related lncRNAs in triple-negative breast cancer patients based on TCGA database

目的基于美国癌症基因组图谱(The Cancer Genome Atlas,TCGA)数据库分析影响三阴性乳腺癌(triple-negative breast cancer,TNBC)预后的铁死亡相关长链非编码RNA(long non-coding RNA,lncRNA),并建立TNBC预后预测模型。方法从TCGA下载TNBC样本的转录组数据及临床信息数据。用R语言limma包筛选乳腺癌差异表达基因,survival包筛选TNBC生存时间相关基因,并与搜集到的382个铁死亡基因取交集,获得与TNBC预后相关的铁死亡基因。采用Pearson法进行共表达分析以确定与铁死亡相关的lncRNA。采用Cox回归分析来确定生存相关的lncRNA和预后因素。LASSO回归分析构建TNBC预后回归模型,受试者工作特征(receiver operating characteristic,ROC)曲线分析该模型对预后的预测价值。结果单因素Cox回归分析显示,17个差异表达的lncRNA与TNBC患者生存时间相关(均P<0.05)。采用LASSO回归分析成功构建由6个铁死亡相关lncRNA(SGMS1-AS1、AC015908.2、LINC01014、AC083967.1、TTC39A-AS1和AL353708.3)构成的TNBC风险预测模型。计算每个样本的风险评分。Kaplan-Meier法分析显示,风险评分可以有效区分低风险患者和高风险患者(P<0.05)。该模型预测TNBC患者1、2和3年总生存率的ROC曲线下面积分别为0.808、0.840和0.807。结论基于TCGA数据库共筛选出17个铁死亡相关lncRNA与TNBC预后相关。基于SGMS1-AS1、AC015908.2、LINC01014、AC083967.1、TTC39A-AS1和AL353708.3这6个铁死亡相关lncRNA构建的模型可较好地预测TNBC患者预后,提示铁死亡相关lncRNA与患者预后具有一定的相关性。

Objective To analyze ferroptosis-related long non-coding RNAs(lncRNAs)affecting the prognosis of triple-negative breast cancer(TNBC)patients based on The Cancer Genome Atlas(TCGA)database,and to develop a prognostic model for TNBC.Methods Transcriptome data and clinical information data of TNBC samples were downloaded from TCGA.The limma package of R language was used to screen the differentially expressed genes in breast cancer,and the survival package was used to screen for TNBC survival related genes,and intersected with the 382 ferroptosis-related genes collected to obtain ferroptosis-related genes associated with TNBC prognosis.Co-expression analysis was performed using the Pearson method to identify lncRNAs associated with ferroptosis.Cox regression analysis was used to identify survival-associated lncRNAs and prognostic factors.LASSO regression model was constructed for TNBC prognosis by regression analysis,and the receiver operating characteristic(ROC)curve was used to analyze the prognostic value of the model.Results Seventeen differentially expressed lncRNAs were associated with prognostic survival of TNBC patients in univariate Cox regression analysis(all P<0.05).The TNBC risk prediction model consisting of six ferroptosis-related lncRNAs(SGMS1-AS1,AC015908.2,LINC01014,AC083967.1,TTC39A-AS1 and AL353708.3)was successfully constructed using LASSO regression analysis.The risk score of each sample was calculated,and Kaplan-Meier analysis showed that the risk scores could effectively distinguish low-risk patients from high-risk patients(P<0.05).The area under the ROC curves for the model to predict the 1-,2-and 3-year overall survival rates of TNBC patients were 0.808,0.840 and 0.807,respectively.Conclusions A total of 17 ferroptosis-related lncRNAs were screened to be associated with TNBC prognosis based on TCGA database.The model constructed based on six ferroptosis-related lncRNAs,SGMS1-AS1,AC015908.2,LINC01014,AC083967.1,TTC39A-AS1 and AL353708.3,can predict the prognosis of TNBC patients,indicating that ferroptosis-related lncRNAs are correlated with the prognosis of TNBC patients.