目的:探讨铜死亡相关的LncRNAs在肝细胞癌(HCC)中的预后价值并构建风险模型,及其在HCC中突变负荷及相关药物的选择,为提出新的HCC治疗方案奠定基础.方法:从癌症基因组谱(TCGA)数据库下载并整合了HCC患者转录组数据、临床数据及突变负荷.通过单因素Cox回归分析筛选出与HCC预后相关的LncRNA.然后使用多因素Cox分析对模型进行构建.通过R软件对肝细胞癌铜死亡预后模型进行分组,并且进行Kaplan-Meier生存分析.使用R语言对铜死亡预后模型进行风险曲线、生存分析、无进展生存期及主成分分析图的绘制,以此来对最佳预后模型进行验证.并使用了ROC曲线、C-index曲线和列线图对模型的预后因素进行了评估.随后进行差异基因进行基因本体论(GO)、京都基因和基因组百科全书(KEGG)富集分析.我们计算了泛癌数据中TMB状态与基因表达之间的相关性,免疫功能相关性分析以及筛选出对HCC潜在药物治疗的敏感.结果:通过单因素Cox回归分析、LASSO回归及多因素Cox回归分析共筛选4 个铜死亡相关基因LncRNA构建预后模型.使用预后模型对样本进行生存分析发现高低风险两组患者明显存在生存差异,预后模型风险评分可以独立于其他临床性状作为独立预后因子,并且风险评分随着分期而增加.随后进行差异基因进行基因本体论(GO)、京都基因和基因组百科全书(KEGG)富集分析.计算泛癌数据中TMB状态与基因表达之间的相关性,免疫相关功能分析以及筛选出对HCC潜在药物治疗的敏感性.结论:基于铜死亡基因的HCC预后模型具有较好的预测效能,该模型中的铜死亡基因为HCC靶向治疗提供了新的治疗靶点.
Objective:To investigate the prognostic value of copper death-related LncRNAs in hepatocellular carcinoma(HCC)and construct a risk model,as well as their mutation burden and related drug selection in HCC,so as to lay the foundation for new HCC treatment.Methods:The transcriptome data,clinical data and mutation burden of HCC patients were downloaded and integrated from the Cancer Genome Atlas(TCGA)database.Univariate Cox regression analysis was used to screen LncRNA related to HCC prognosis.Multivariate Cox analysis was then used to construct the model.The prognostic models of HCC were grouped by R software,and Kaplan-Meier survival analysis was performed.The risk curve,survival analysis,progression-free survival and principal component analysis were drawn by R language to verify the best prognostic model.ROC curve,C-index curve and nomogram were used to evaluate the prognostic factors of the model.Subsequently,differentially expressed genes were subjected to Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis.We calculated the correlation between TMB status and gene expression in pan-cancer data,analyzed the correlation of immune function and screened for sensitivity to potential drug therapy in HCC.Results:A total of 4 LncRNAs with cuproptosis genes were screened to construct a prognostic model by univariate Cox regression analysis,Lasso regression and multivariate Cox regression analysis.The survival analysis of the samples using the prognostic model found that there were significant differences in survival between the high and low risk groups.The prognostic model risk score could be independent of other clinical traits as an independent prognostic factors,and risk scores increased with stage.Differential genes were subsequently subjected to Gene Ontology(GO),Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis.We calculated correlations between TMB status and gene expression in pan-cancer data,immune-related functional analysis,and screened out sensitivity to potential drug treatments for HCC.Conclusion:The prognostic model of primary liver cancer based on copper death gene has good predictive performance,and the copper death gene in this model provides a new therapeutic target for targeted therapy of primary liver cancer.