胃癌预后相关铁死亡基因筛选及预后预测模型构建

Screening of ferroptosis-related prognostic genes of gastric cancer and construction of a prognostic model

目的运用生物信息学方法筛选与胃癌预后相关铁死亡基因,构建铁死亡基因相关胃癌预后预测模型。方法①与胃癌预后相关的铁死亡基因筛选:从癌症基因组图谱(TCGA)数据库中获取胃癌基因微阵列图谱及相关患者的临床资料。采用R软件筛选癌组织、癌旁组织中差异表达的铁死亡基因以及与总体生存率有关的预后基因。对其取交集得到与胃癌预后相关的铁死亡基因。采用基因集富集分析(genesetenrichmentanalysis,GSEA)软件(https//www.gsea-msigdb.org/gsea/index.jsp)分析胃癌预后相关铁死亡基因高表达时的富集通路。②胃癌预后预测模型构建与验证:运用LassoCox回归分析法构建基因相关的胃癌预后预测模型并进行验证。结果与癌旁组织比较,胃癌组织中29个铁死亡基因表达升高、12个铁死亡基因表达降低。与胃癌预后相关的铁死亡基因为NFE2L2、SLC1A5。NFE2L2主要参与化学刺激检测、膜电位调节等生物学功能,SLC1A5主要参与金属离子传输、丝氨酸苏氨酸蛋白激酶活性调节等生物学功能。胃癌预后预测模型=e^((-0.315×NFE2L2)+(-0.161×SLC1A5))。该模型预测胃癌患者预后的第1、2、3年ROC曲线下面积分别为0.561、0.587、0.615。预后评分对高、低风险组患者预后的区分程度较好;独立预后分析提示该模型预后评分是胃癌的独立预后因素。结论胃癌组织中与预后相关的铁死亡基因为NFE2L2、SLC1A5。得到胃癌预后预测模型=e^((-0.315×NFE2L2)+(-0.161×SLC1A5)),根据模型测算得到的预后评分对胃癌患者预后的预测价值较高。

Objective To screen out the ferroptosis-related prognostic genes of gastric cancer and to construct a ferroptosis genes-related prognostic model through bioinformatics method.Methods①To screen out ferroptosis-related genes associated with prognosis of gastric cancer:The gene microarray and related clinical data of gastric cancer were download from The Cancer Genome Atlas(TCGA)database.R software was used to screen out ferroptosis-related differentially expressed genes between cancer and paracancer tissues,as well as prognostic genes related to overall survival.The intersectional genes were obtained and their biological functions were analyzed.The Gene Set Enrichment Analysis(GSEA)software(https//www.gsea-msigdb.org/gsea/index.jsp)was utilized to analyze the enrichment pathways of ferroptosis genes related to the prognosis of gastric cancer of high expression.②To construct and verify prognostic model of gastric cancer:A gene-related prognostic model of gastric cancer was constructed and validated by Lasso Cox regression analysis.Results Compared with paracancer tissues,the expression of 29 ferroptosis-related genes increased and the expression of 12 ferroptosis-related genes decreased in the gastric cancer tissues.Among them,NFE2L2 and SLC1A5 were related to the prognosis of gastric cancer.NFE2L2 mainly participated in the biological functions such as detection of chemical stimulus and regulation of membrane potential,while SLC1A5 mainly participated in the biological functions such as metal ion transport and regulation of protein serine and threonine kinase activity.The prognostic model of these genes was e^((-0.315×NFE2L2)+(-0.161×SLC1A5)).The area under ROC curve predicted by this model was 0.561,0.587 and 0.615 in the first,second and third years,respectively.The prognostic model had a good distinction between the high and low risk groups.Independent prognostic analysis suggested that the prognostic score of the model was an independent prognostic factor for gastric cancer.Conclusions NFE2L2,SLC1A5 are ferroptosis-related prognostic genes of gastric cancer,and the prognostic model of these genes is e^((-0.315×NFE2L2)+(-0.161×SLC1A5)).The prognostic model has a high predictive value for the prognosis of gastric cancer patients.