何 元,吕 舰,王志华.基于TCGA数据分析黑色素瘤中的可变剪切事件及预后模型建立[J].肿瘤学杂志,2020,26(10):891-896.
基于TCGA数据分析黑色素瘤中的可变剪切事件及预后模型建立
Prognostic Model for Melanoma Based on TCGA Data Analysis of Alternative Splicing Events
投稿时间:2019-12-02  
DOI:10.11735/j.issn.1671-170X.2020.10.B008
中文关键词:  可变剪切  黑色素瘤  TCGA
英文关键词:alternative splicing  melanoma  TCGA
基金项目:
作者单位
何 元 武汉大学人民医院 
吕 舰 武汉大学人民医院 
王志华 武汉大学人民医院 
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中文摘要:
      摘 要:[目的] 探讨可变剪切事件与黑色素瘤预后的相关性。[方法] 471例黑色素瘤患者的临床信息下载自TCGA数据库,与患者对应的可变剪切事件下载自TCGA SpliceSep数据库。采用单因素Cox回归分析筛选预后相关的可变剪切事件;采用Lasso回归分析构建预后模型,并计算黑色素瘤患者的风险值,对高低风险组绘制生存曲线,ROC曲线和风险曲线;随后采用单因素和多因素Cox回归分析进行独立预后分析。采用Metascape在线工具对预后相关的可变剪切基因进行富集分析。[结果] 设置阈值为P<0.05,筛选得到的预后相关的可变剪切事件共有1238例。Lasso回归表明,采用MTMR14│63114│ES和BATF2│16723│AP的可变剪切事件PSI值作为预后模型,高风险组患者的生存时间减少,死亡人数增加。此外,预后模型作为独立预后因子可准确预测黑色素瘤患者的预后状况。与预后相关的可变剪切基因富集的生物学功能主要包括细胞死亡的调节,蛋白复合体组装的调节,GTP酶活性的调节,核质运输和DNA修复。[结论] 预后相关的可变剪切事件可作为预后模型,较准确地预测黑色素瘤的预后状况。
英文摘要:
      Abstract:[Objective] To establish a prognostic model for melanoma based on alternative splicing events. [Methods] Clinical information of 471 melanoma cases was downloaded from The Cancer Genome Atlas(TCGA),and alternative splicing events corresponding to those cases were downloaded from TCGA SpliceSep. Prognostic-related alternative splicing events were screened by univariate Cox regression analysis. The prognostic model was constructed by Lasso regression analysis,and risk values for melanoma patients were calculated. Survival curves,ROC curves and risk curves were plotted for high and low risk groups. Independent prognostic analysis was then performed by univariate and multivariate Cox regression analysis. The enrichment analysis of prognostic-related alternative splicing events were performed by the Metascape online tool. [Results] The threshold was set to P<0.05,and a total of 1238 prognostic-related alternative splicing events were identified by screening. Lasso regression showed that the PSI values of MTMR14-63114-ES and BATF2-16723-AP were used as prognostic models,and the survival time of patients in the high-risk group decreased and the number of deaths increased. In addition,the prognostic model was an independent prognostic factor to predict the prognosis of melanoma patients. The biological functions of prognosis-related alternative splicing were mainly enriched by positive regulation of cell death,regulation of protein complex assembly,regulation of GTPase activity,nucleocytoplasmic transport and DNA repair. [Conclusion] Prognosis-related alternative splicing events can be used to predict the prognosis of melanoma.
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