肺腺癌中免疫相关lncRNA的筛查表达与预后分析

Screening of Immune-Related lncRNAs and Analysis of Their Expression and Prognosis in Lung Adenocarcinoma

目的筛查肺腺癌免疫相关lncRNA,并分析其在肺腺癌中的表达及对患者预后的影响。方法自美国TCGA数据库筛选肺腺癌患者的转录数据和临床资料;使用美国Cytoscape软件3.5.0构建免疫-lncRNA共表达网络获得免疫相关的lncRNA;采用单变量Cox回归分析分配风险评分,筛选预后相关的lncRNA,GraphPad Prism 8软件进行Kaplan-Meier生存分析,多变量Cox回归分析预测患者生存的独立预后因素;使用R3.6.1软件和limma包进行主成分分析;基因组富集分析各组的功能注释。结果数据库挖掘获得14142个lncRNA和331个免疫相关基因,关联分析共筛选出1133个免疫相关的lncRNA;单因素COX回归分析发现15个免疫相关lncRNA与肺腺癌预后相关,多因素Cox回归分析发现其中6个免疫相关的lncRNA(AL161431.1、AC079949.2、LINC00707、AC010980.2、AC068338.3、AC123595.1)是肺腺癌患者生存的独立预后因素,而风险分数是与总生存期相关的独立预后因素;6个免疫相关的lncRNA中低风险组总体生存期较高风险组显著延长(P<0.0001);主成分分析显示,高、低风险组的风险值有显著差异;基因富集分析结果显示高、低风险组在免疫应答通路中均有富集。结论成功筛选出6个免疫相关的lncRNA,且其可预测肺腺癌患者的预后。

Objective To screen immune-related lncRNAs in lung adenocarcinoma,and to analyze their expression and influence on the prognosis.Methods The transcriptional and clinical data of lung adenocarcinoma patients were screened from the TCGA database.An immune-lncRNA co-expression network was constructed using the Cytoscape software 3.5.0 to obtain the immune-related lncRNAs.The univariate Cox regression analysis was conducted to assign risk scores and to screen prognosis-related lncRNAs.The GraphPad Prism 8 software was used for Kaplan-Meier survival analysis.The multivariate Cox regression analysis was performed to predict independent prognostic factors for patient survival.The R3.6.1 software and limma package was used for principal component analysis.The genome enrichment analysis was carried out for functional annotations between the two groups.Results A total of 14142 lncRNAs and 331 immune-related genes were obtained,and 1133 immune-related lncRNAs were screened out by association analysis(P<0.001).Univariate COX regression analysis showed that 15 immune-related lncRNAs were correlated with the prognosis of lung adenocarcinoma.Multivariate COX regression analysis demonstrated that 6 immune-related lncRNAs(AL161431.1,AC079949.2,LINC00707,AC010980.2,AC068338.3 and AC123595.1)were independent prognostic factors for survival in patients with lung adenocarcinoma.Risk score was an independent prognostic factor for overall survival.According to the above 6 immune-related lncRNA expression risk scores,the overall survival in the low-risk group was longer than that in the higher-risk group(P<0.0001).Principal component analysis showed that the risk values of the two groups were significantly different.Gene enrichment analysis revealed that the lncRNAs were enriched in the immune response pathway in both high-risk and low-risk groups.Conclusion Six immune-related lncRNAs obtained in this study can predict the prognosis of patient with lung adenocarcinoma.