铁死亡相关lncRNA在神经胶质瘤的预后价值分析

Analysis of Prognostic Values of Ferroptosis-related lncRNA in Glioma

关键词:  神经胶质瘤  铁死亡  lncRNA  生物信息学  生物标志物

Key words:  glioma  ferroptosis  lncRNA  bioinformatics  biomarker

摘要:

通过分析癌症基因组图谱(The Cancer Genome Atlas，TCGA)数据库的神经胶质瘤患者的转录组数据与临床数据，应用基因共表达法、单因素Cox回归法筛选与预后有关的铁死亡相关长非编码RNA(long non-coding RNA,lncRNA)，根据LASSO Cox回归分析与筛选出的lncRNA在样本中的表达情况，将样本分为高、低风险两组，通过单因素及多因素独立预后分析、受试者工作特征曲线(Receiver Operating Characteristic Curve，ROC Curve)、Kaplan-Meier生存曲线、风险曲线、基因富集分析(Gene Set Enrichment Analysis，GSEA)等方法评估铁死亡相关lncRNA在神经胶质瘤预后中的价值及临床意义，通过TIMER、CIBERSORT、CIBERSORT-ABS等方法分析免疫浸润情况，进一步对免疫功能、免疫检查点以及N6-甲基腺苷(m⁶A)甲基化差异进行分析。结果获得预后相关的铁死亡相关lncRNA共14个。单因素及多因素独立预后分析、ROC曲线结果表明,铁死亡相关lncRNA可作为独立的预后因子。Kaplan-Meier生存曲线与风险曲线表明，高风险组的生存时间更短。GSEA结果显示，高风险组中同种异体移植排斥、DNA复制、错配修复等显著活跃，而低风险组长程增强效应、磷脂酰肌醇信号系统显著活跃等，此外，基于不同方法高、低风险组的免疫浸润情况也有所差异，高风险组的大部分免疫检查点表达显著高于低风险组，m⁶A相关基因的表达在高、低风险组中也具有显著性差异。本研究表明，铁死亡相关lncRNA与神经胶质瘤患者的生存密切相关，可作为神经胶质瘤预后新的生物标志物和潜在的治疗靶点。

Abstract:

The transcriptomic data and clinical data of glioma patients of The Cancer Genome Atlas (TCGA) database were analyzed,and gene co-expression,univariate Cox hazard analysis were utilized to screen ferroptosis-related long non-coding RNA (lncRNA) associated with prognosis.According to LASSO Cox regression analysis and the screened lncRNA expression in the samples,the samples were divided into high and low risk groups.The value and clinical significance of iron death-related lncRNA in the prognosis of glioma were evaluated by univariate and multivariate independent prognostic analysis,Receiver Operating Characteristic Curve (ROC Curve),Kaplan-Meier survival curve,risk curve,and Gene Set Enrichment Analysis (GSEA).The immune infiltration was analyzed by TIMER,CIBERSORT,CIBERSORT-ABS and other methods,and the differences in immune function,immune checkpoint and methylation of N6-methyladenosine (m⁶A) were further analyzed.A total of 14 ferroptosis-related lncRNA associated with prognosis were obtained. The results of univariate Cox regression analysis,multivariate Cox regression analysis and ROC curves suggested that iron mortality associated lncRNA could be used as independent prognostic factors.Kaplan-Meier survival curve and risk curve showed that the survival time of the high-risk group was shorter.GSEA results showed that allograft rejection,DNA replication,mismatch repair,etc.were significantly active in the high-risk group,while the long-range enhancement effect and phosphatidylinositol signaling system were significantly active in the low-risk group.In addition,there were differences in immune infiltration in the high-risk group based on different methods.The expression of immune checkpoints in high risk group was significantly higher than that in low risk group,and most of the immune checkpoints in high risk group were significantly higher than those in low risk group.The expression of m⁶A-related genes was also significantly different in the high-risk and low-risk groups.This study revealed that ferroptosis-related lncRNA are closely related to the survival of patients with glioma and can be used as new biomarkers and potential therapeutic targets for glioma prognosis.