摘要
目的:基于内质网应激(ERS)相关基因构建结直肠癌(CRC)预后风险预测模型,并探讨该模型预测CRC预后的价值.方法:从TCGA数据库中下载CRC组的基因表达数据和临床信息,通过LASSO回归以及多因素Cox回归分析,设计一个以ERS相关基因为中心的预后风险预测模型.利用该模型预测CRC患者的预后风险和免疫反应,并用ROC曲线对风险预测模型进行效能评估.结果:在455例CRC基因表达数据中找到255个ERS相关基因,利用多因素Cox回归筛选出HSPA1 A、MAGEA3、ATP2A1、DNAJB2、DNAJC3、EIF2B5、FLOT1、GET4、HERPUD2、STC2、TMUB1 等 11 个与预后相关的基因,并构建预后风险预测模型,风险评分=0.151 × HSPA1A+0.240 × MAGEA3+1.715 × ATP2A1+1.162× DNAJB2-0.563 × DNAJC3+1.127 × EIF2B5+0.653 × FLOT1-1.580 × GET4+1.684 × HERP-UD2+0.260 × STC2+0.710× TMUB1.风险评分越高,患者的预后、免疫反应和药物敏感性越差,肿瘤突变负荷(TMB)评分也越低.与TNM分级相比,预后风险预测模型一致性指数和ROC曲线下面积(AUC=0.78)更高.结论:ERS相关基因预后风险预测模型对CRC的预后具有较好的预测效能,且对免疫治疗有一定的指导作用.
Abstract
Objective:To construct a prognostic risk prediction model for colorectal cancer(CRC)based on endoplasmic reticulum stress(ERS)-related genes,and to evaluate the value of the model in predicting the prognosis of CRC.Methods:The gene data and clinical information of CRC group were downloaded from the TCGA database,and a prognostic risk prediction model based on ERS-related genes was designed by LASSO regression and multivariate Cox regression analysis.The model was used to predict the prognostic risk and immune response of CRC pa-tients,and the ROC curve was used to evaluate the efficacy of the risk prediction model.Re-sults:A total of 255 ERS-related genes were found in the data of 455 CRC cases,and 11 prognosis-related genes,including HSPA1A,MAGEA3,ATP2A1,DNAJB2,DNAJC3,EIF2B5,FLOT1,GET4,HERPUD2,STC2 and TMUB1,were screened by multivariate Cox regression,and a prognostic risk prediction model was constructed,with risk score=0.151 × HSPA1A+0.240 × MAGEA3+1.715 × ATP2A1+1.162 × DNAJB2-0.563 × DNAJC3+1.127 × EIF2B5+0.653 × FLOT1-1.580 × GET4+1.684 × HERPUD2+0.260 × STC2+0.710 × TMUB1.Higher risk scores were associ-ated with worse prognosis,immune response,drug sensitivity in patients and the lower the TMB score.Compared to traditional TNM staging,the area under the ROC curve(AUC=0.78)and C in-dex of the prognostic risk prediction model were higher.Conclusion:The prognostic risk predic-tion model of ERS-related genes has a good predictive effect on the prognosis of CRCand pro-vides guidance for the application of immunotherapy.