基于氧化应激因子构建结肠癌的预后风险标志物及其临床意义

Construction of prognostic risk markers of colon cancer based on oxidative stress factors and its clinical significance

目的探讨结肠癌中氧化应激相关的特征基因并筛选预后标志物。方法结合氧化应激相关基因与结肠癌的转录组数据,利用Cox回归分析筛选预后标志物并构建预后模型。通过生存分析和受试者操作特征曲线分析模型的有效性。根据风险评分中位数区分高、低风险组。利用Cox分析验证风险评分的独立性,随后构建列线图。最后,分析高、低风险组的预后差异、免疫微环境差异以及免疫治疗反应程度。结果最终筛选出9个氧化应激相关基因(CPT2、FARS2、RYR2、MSRA、PPARGC1a、LEP、AGT、EPO、STK25),并以此构建预后模型。生存分析和受试者操作特征曲线结果表明,该模型能很好地预测结肠癌风险(P<0.05,曲线下面积>0.6),且风险评分可作为独立预后因子(P<0.001)。此外,高风险组中TP53突变频率更高(P<0.0001)。同时,低风险组患者免疫表型评分高于高风险组(P<0.05),肿瘤免疫功能障碍和排斥评分低于高风险组(P<0.05)。诺莫图预测的结肠癌患者1、3年总生存期与实际总生存期非常接近。结论氧化应激相关的9个基因是结肠癌预后标志物,这些预后标志物可能是治疗结肠癌患者新的潜在靶点。

Objective To investing the feature genes related to oxidative stress in colon cancer and screen prognostic markers of colon cancer.Methods Oxidative stress related genes were combined with transcrip-tomic data of colon cancer to screen prognostic markers,followed by construction of a prognostic model using Cox regression analysis.The validity of the model was analyzed by survival analysis and receiver operating characteristic curves.High-and low-risk groups were distinguished according to the median risk-score.Cox analysis was used to verify the independence of risk-score,followed by the construction of nomograms.Finally,the prognostic differences,immune microenvironment differences,and the degree of response to immunotherapy between the high-and low-risk groups were analyzed.Results Nine oxidative stress related genes(CPT2,FARS2,RYR2,MSRA,PPARGC1a,LEP,AGT,EPO,STK25)were screened and used to con-struct a prognostic model.The results of survival analysis and receiver operating characteristic curve showed that the model could predict risk of colon cancer well(P<0.05,area under curve>0.6).Risk-score could be used as an independent prognostic factor(P<0.001).Additionally,the frequency of TP53 mutations was high-er in the high-risk group(P<0.0001).Meanwhile,the immunopheno scores was higher in the low-risk group than in the high-risk group(P<0.05).And tumor immune dysfunction and exclusion scores in the low-risk group was lower than that in the high-risk group(P<0.05).Finally,The overall survival of colon cancer patients predicted by nomograms at 1 and 3 years is very close to the actual overall survival.Conclusion This study identified oxidative stress related prognostic markers for colon cancer,which may be new potential therapeutic targets for the treatment of colon cancer patients.