构建铁死亡相关的lncRNAs预测肝细胞癌预后模型

Ferroptosis-related lncRNAs model predicts the prognosis of hepatocellular carcinoma

目的通过铁死亡相关lncRNAs差异基因构建反映肝细胞(hepatocellular carcinoma,HCC)患者生存情况的预后模型。方法我们从TCGA和FerrDb数据库中收集了与铁死亡相关的lncRNA表达谱以及临床病理情况。通过对总生存期(overall survival,OS)的共表达分析,研究铁死亡相关lncRNAs与HCC患者生存的关系。利用Cox回归分析和LASSO算法,构建22个差异表达的lncRNAs的预后模型。结果Kaplan-Meier分析显示,高风险的lncRNAs谱与HCC的不良预后有关。我们的风险评估模型在预测HCC的预后方面优于传统的临床数据。GSEA揭示了高风险组和低风险组个体的免疫和肿瘤相关通路。此外,TCGA显示T细胞功能,包括B细胞、细胞溶解、巨噬细胞、MHC-I类、肥大细胞、中性粒细胞、NK细胞、辅助T细胞、Ⅰ型-IFN和Ⅱ型-IFN,在高危组和低危组之间有明显差异。免疫检查点如TNFSF18、IDO2、CD276、NRP1和TNFSF4在两个风险组之间也有不同表达。选取MIR4435-2HG、SNHG4、PRRT3-AS1和PTOV1-AS1在肝癌细胞中进行验证,结果显示这四个基因在肝癌细胞中的表达上调。结论我们的研究结果有望为HCC诊断、靶向治疗及预后评估提供新的研究方向。

Objective To construct a prognostic model reflecting hepatocellular carcinoma(HCC)patient survival through differentially expressed ferroptosis-related lncRNAs.Methods We gathered lncRNA expression profiles associated with ferroptosis and clinical pathological data from TCGA and FerrDb databases.Co-expression analysis of overall survival(OS)investigated the relationship between ferroptosis-related lncRNAs and HCC patient survival.A prognostic model of 22 differentially expressed lncRNAs was built using Cox regression analysis and the LASSO algorithm.Results Kaplan-Meier analysis revealed that a high-risk lncRNAs profile was associated with poor prognosis in HCC.Our risk assessment model outperformed conventional clinical data in predicting the prognosis of HCC.GSEA revealed immune and tumor-related pathways in individuals in the high-and low-risk groups.In addition,TCGA showed that T cell functions,B cells,cytolytic,macrophages,MHC-class-I,mast cells,neutrophils,NK cells,helper T cells,Type-Ⅰ-IFN and Type-Ⅱ-IFN were significantly different between high-and low-risk groups.Immune checkpoints such as TNFSF18,IDO2,CD276,NRP1 and TNFSF4 were also differentially expressed between the two risk groups.Selected MIR4435-2HG,SNHG4,PRRT3-AS1 and PTOV1-AS1 were validated in hepatocellular carcinoma cells,and the results showed that the expression of these four genes was upregulated in hepatocellular carcinoma cells.Conclusion The findings of our study are anticipated to offer novel research avenues for the diagnosis,targeted therapy and prognostic assessment of HCC.