通过生物信息学分析筛选影响胃腺癌患者预后的铁死亡相关基因

Screening Ferroptosis Related Genes Influencing Prognosis of Gastric Adenocarcinoma Through Bioinformatics Analysis

目的利用生物信息学分析筛选影响胃腺癌患者预后的铁死亡相关基因(ferroptosis-related genes,FRGs)。方法通过TCGA数据库下载胃腺癌的基因表达和临床数据,使用R软件获取铁死亡相关差异表达基因和预后相关基因,并最终获得影响胃腺癌预后的FRGs。使用LASSO回归分析构建风险模型,计算风险值。通过受试者工作特征曲线(receiver operating characteristic curve,ROC)比较患者5年生存率,使用单因素和多因素生存分析筛选独立预后因素。对与胃腺癌预后相关的FRGs进行通路富集分析。结果从数据库中共得到443例患者临床信息,407个数据集。通过比较发现163个在胃腺癌中差异表达的FRGs,25个预后相关的FRGs,取交集后发现14个影响胃腺癌患者预后的FRGs。使用LASSO回归分析,最终筛选出8个FRGs(NOX4、NOX5、GLS2、MYB、TGFBR、DUSP1、SLC1A4、NF2),构建风险模型。依据患者的风险值,区分高、低风险组,发现高风险组患者总生存率明显低于低风险组。通过多因素生存分析发现年龄、T分期和风险值可以作为独立预后因素。ROC曲线发现使用预后相关FRGs构建的风险模型能够较好地预测患者5年生存率(AUC=0.668)。对高、低风险组患者中的差异基因进行通路富集分析,发现差异基因可能与细胞外基质组成和细胞外结构构成、PI3K-Akt等基因通路有关。结论FRGs(NOX4、NOX5、GLS2等)影响胃腺癌患者的预后,为胃腺癌的铁死亡研究提供了新的线索。

Objective To screen out prognosis-related ferroptosis related genes(FRGs)of gastric adenocarcinoma patients by using bioinformatics analysis.Methods The gene expression and clinical data of gastric adenocarcinoma were download from the TCGA database,and the data were analyzed to obtain differentially expressed genes of FRG and prognosis-related genes by R software,and finally obtain prognosis-related FRGs in gastric adenocarcinoma.LASSO regression analysis was used to build a risk model and assess the sensitivity of the model by receiver operating characteristic curve(ROC).COX analysis was used to screen independent prognostic factors,and pathway enrichment analysis was performed for prognosis-related FRGs.Results A total of 443 patients’clinical information and 407 data sets were obtained from the database.Totally,163 differentially expressed FRGs and 25 prognosis-related FRGs were found.After the intersection,14 prognosis-related FRGs were found.Using LASSO regression analysis,8 FRGs(NOX4,NOX5,GLS2,MYB,TGFBR,DUSP1,SLC1 A4,NF2)were screened out,which was used to construct a risk model by calculating the risk.According to the risk value,the patients were divided into two groups:high-risk group and low-risk group.We found that the overall survival rate of patients in the high-risk group was significantly lower than that in the low-risk group.Through COX analysis,it was found that age,T stage and risk value could be used as independent prognostic factors.The ROC curve found that the risk model could well predict five-year survival(AUC=0.668).Pathway enrichment analysis showed that the differential genes related to the composition of extracellular matrix and structure,PI3 K-Akt and other gene pathways in the high-and low-risk groups.Conclusion Our results indicate that FRGs(NOX4,NOX5,GLS2,etc.)affect the prognosis of gastric cancer patients.It also provides new clues for the study of ferroptosis in gastric adenocarcinoma.