一种基于m7G RNA修饰相关基因的乳腺癌预后预测模型的构建和验证  

Construction and validation of a novel model for predicting prognosis of breast cancer patients based on m7G RNA modification-related genes

作　　者：李健[1] 刘阳[2] 刘飞[1] 王颜 LI Jian;LIU Yang;LIU Fei;WANG Yan(Breast Disease Diagnosis and Treatment Center,the Affiliated Taian City Central Hospital of Qingdao University,Tai'an 271000,China;Department of Hepatobiliary and Pancreatic Surgery,the Affiliated Taian City Central Hospital of Qingdao University,Tai'an 271000,China;Department of Applied Mathematics,School of Information Science and Engineering,Shandong Agricultural University,Tai'an 271000,China)

机构地区：[1]青岛大学附属泰安市中心医院乳腺疾病诊疗中心,山东泰安271000 [2]青岛大学附属泰安市中心医院肝胆胰腺外科,山东泰安271000 [3]山东农业大学信息科学与工程学院应用数学系,山东泰安271000

出　　处：《中国现代普通外科进展》2023年第12期933-938,共6页Chinese Journal of Current Advances in General Surgery

摘　　要：目的:建立并验证一种基于N7甲基鸟苷(m7G)RNA甲基化修饰相关基因的乳腺癌预后预测模型。方法:检测31种m7G RNA甲基化相关的关键调控因子在乳腺癌组织中的表达模式。下载癌症基因组图谱(TCGA)和基因表达综合数据库(GEO)中的乳腺癌患者的m RNA基因表达和临床预后数据。通过单变量Cox回归分析评估每个m7G相关基因对生存的预后价值。应用最小绝对收缩和选择算子(LASSO)回归方法,构建基于m7G甲基化调节基因的乳腺癌预后风险模型。通过基因集富集分析(GSEA)阐述BC高危人群的主要作用机制。基于m7G建立预后列线图,分别在TCGA和GEO队列中进行验证。结果:构建基于7个m7G甲基化调节基因的预后风险模型。高危组总生存率(OS)明显低于低危组(P<0.001)。GSEA分析表明,在高危人群中“细胞周期”是最重要的致癌通路。利用训练集TCGA队列的风险评分及临床特征,构建了预后列线图,校准曲线和决策曲线分析(DCA)表明其一致性和预测效能很好,并于GEO队列中进行了验证。结论:基于m7G相关基因的预后模型对乳腺癌的预后具有预测作用,可用于指导乳腺癌患者的个体化治疗。Objective:The aim of this study was to determine the development and validation of a prognostic prediction model based on genes associated with N7 methylguanosine(m7G)RNA methylation modifications in breast cancer(BC)patients.Methods:We explored the expression patterns of 31 key m7G RNA methylation-related regulators in breast cancer tissues and their prognostic significance.First,we downloaded and analyzed the mRNA gene expression and clinical prognostic data from The Cancer Genome Atlas(TCGA)and Gene Expression Gene Expression(GEO)databases.The prognostic value of each m7G-related gene for survival was assessed by using univariate Cox regression analysis.A prognostic risk model based on m7G methylation-regulated genes was then constructed by applying the least absolute shrinkage and selection operator(LASSO)regression method.Patients were divided into high-risk and low-risk groups according to median risk scores,and the differences in overall survival(OS)between high-and low-risk groups were compared.Then,gene set enrichment analysis(GSEA)analysis was performed to elaborate the main mechanisms of action in the BC high-risk group.Finally,a prognostic nomogram based on m7G was constructed and validated in TCGA and GEO cohorts respectively.Results:A prognostic risk model based on seven m7G methylation-regulated genes was constructed.The overall survival(OS)was significantly lower in the high-risk group than in the low-risk group(P<0.001).GSEA analysis showed that the"cell cycle"was the most important pathways in the high-risk group.Using risk scores and clinical characteristics of the training set TCGA cohort,prognostic nomogram was constructed,and calibration curves and decision curve analysis(DCA)showed good concordance and predictive efficacy and were validated in the GEO cohort.Conclusion:The prognostic model based on m7G-related genes plays an important prognostic predictive role in breast cancer and can be used to guide the individualized treatment of breast cancer patients.

关 键 词：乳腺癌 m7G RNA甲基化修饰 预后列线图 癌症基因组图谱 基因表达综合数据库 

分 类 号：R737.9[医药卫生—肿瘤]