基于铁死亡相关基因构建结直肠癌预后风险模型

Construction of a Prognostic Risk Model for Coloreetal Cancer based on Ferroptosis-related Genes

目的基于铁死亡相关基因构建预测能力较好的结直肠癌(colorectal cancer,CRC)预后风险模型。方法从UCSC Xena及FerrDb V2数据库获得CRC患者的转录水平、临床数据及最新铁死亡相关基因。利用R语言和单因素COX回归分析筛选出与预后有关的基因,通过LASSO回归结合多因素COX回归分析确立最终的预后风险模型。然后采用R语言“survival”包、“timeROC”包及COX回归对模型进行生存分析及预测能力评估。结果筛选出由NEDD4L、TIMP1、KIF20A、GDF15、ENO3、TERT、MS4A15、HOTAIR 8个铁死亡相关差异基因构建的预后模型。模型将纳入的CRC患者分为两组,两组间的生存预后差异有统计学意义(P<0.05)。受试者工作特征(receiver operating characteristic,ROC)曲线分析结果显示,1、3、5年曲线下面积分别为0.732、0.702、0.738。GO和KEGG分析结果显示,两组间基因在肿瘤进程、炎性反应甚至免疫等功能及通路中富集。免疫相关功能、免疫细胞浸润及免疫检查点在高低风险组之间比较,差异有统计学意义(P<0.05)。结论基于8个铁死亡相关差异基因构建的预后模型对CRC有独立的预后作用,对CRC的预后预测提供了新的思路。

Objective To construct a prognostic risk model for colorectal cancer(CRC)with good prediction ability based on upda-ted ferroptosis-related genes.Methods Transcriptome levels,clinical information and updated ferroptosis-related genes of CRC pa-tients were downloaded from UCSC Xena and FerrDb V2databases.The genes related to prognosis were screened out by R language and univariate COX regression analysis,and the final prognostic risk model was established by LASSO regression combined with multivariate COX regression analysis.Then,survival analysis and the predictive power of the model were assessed by R language"survival"package,"timeROC"package and COX regression.Results There were 8differentially expressed ferroptosis-related genes including NEDD4L,TIMP1,KIF20A,GDF15,ENO3,TERT,MS4A15,HOTAIR which composed of the prognostic risk model.The model divided the CRC patients into two groups,and the difference in survival prognosis was between the two groups was statistically significant(P<0.05).The area under the receiver operating characteristic(R0C)curves of the model in 1,3 and 5 year were 0.732,0.702 and 0.738,respective-ly.The results of CO and KECG analysis showed that the genes between the two groups were enriched in pathways and functions such as tumor process,inflammatory response,and even immunity.Immune-related functions,immune cell infiltration,and immune check-points were significantly different between high and low risk groups(P<0.05).Conclusion The prognostic model constructed based on 8differentially expressed ferroptosis-related genes has an independent prognostic effect on CRC,providing a new way to predict the prog-nosis of CRC.