基于免疫基因组学的结肠腺癌患者预后风险模型的建立  

Construction of prognostic risk model for patients with colon adenocarcinoma based onimmunogenomics analysis

作　　者：陈恩更 陈力[1] 曹高扬 王飞 章玮 周玮[1] 宋章法[1] Chen En-Geng;Chen Li;Cao Gao-Yang;Wang Fei;Zhang Wei;Zhou Wei;Song Zhang-Fa(Department of Anorectal Surgery,Sir Run Run Shaw Hospital,School of Medicine,Zhejiang University,Hangzhou 310016,China)

机构地区：[1]浙江大学医学院附属邵逸夫医院肛肠外科,杭州310016

出　　处：《解放军医学杂志》2020年第9期935-939,共5页Medical Journal of Chinese People's Liberation Army

基　　金：国家自然科学基金(81771502)。

摘　　要：目的探索影响结肠腺癌患者预后的免疫基因,构建结肠腺癌患者的预后风险模型。方法从癌症基因组图谱(TCGA)数据库中获取结肠腺癌患者的RNA-seq数据及临床病例资料。根据组织样本分为肿瘤组与对照组,筛选出差异表达的免疫基因。通过Cox回归分析筛选出与结肠腺癌患者预后相关的免疫基因,并构建预后风险评分模型。计算每例结肠腺癌患者的风险评分,根据中位风险评分将其分为高风险组和低风险组,通过Kaplan-Meier分析及受试者工作特征(ROC)曲线对免疫基因预后风险模型的预测效能进行评价,并对免疫基因预后风险模型与免疫细胞浸润的相关性进行分析。结果肿瘤组与对照组共存在220个差异表达的免疫基因,COX回归分析显示其中CXCL5(CX-C motif chemokine ligand 5)、IGHV5-51(immunoglobulin heavy variable 5-51)、IGKV1-33(immunoglobulin kappa variable 1-33)、CHGA(chromogranin A)、UCN(urocortin)、VIP(vasoactive intestinal peptide)和NR3C2(nuclear receptor subfamily 3 group C member 2)等7个免疫基因与预后相关。构建的免疫基因预后风险评分模型为:风险评分(RS)=0.0050×CXCL5+0.0013×IGHV5-51+0.0221×IGKV1-33+0.0083×CHGA+0.3097×UCN+0.0551×VIP–0.2255×NR3C2。在结肠腺癌患者中,低风险组的总生存率高于高风险组(P<0.001),高风险组和低风险组的5年总生存率分别为49.4%和75.8%。ROC曲线显示AUC为0.741。免疫基因预后模型与B细胞、CD4+T细胞、CD8+T细胞、树突细胞、巨噬细胞及自然杀伤细胞等免疫细胞浸润相关。结论构建了结肠腺癌患者的免疫基因预后风险评分模型,系统评价和验证了该模型在结肠腺癌患者个体化治疗中的重要性,为寻找新的免疫治疗靶点提供了方向。Objective To analyze the immune genome environment of colon adenocarcinoma(COAD),find the immune genes related to the prognosis of COAD patients,and construct a prognostic risk score model to provide a basis for prognosis evaluation and individual diagnosis and treatment of COAD patients.Methods The RNA-seq data and clinical data of COAD patients were downloaded from TCGA(The Cancer Genome Atlas)database.Samples were divided into Tumor group and Normal group according to the type of tissues,and the differentially expressed immune genes were screened by R language.The immune genes related to the prognosis of COAD patients were screened by Cox regression analysis,and the prognostic risk score model was constructed.The COAD patients were divided into high-risk group and low-risk group according to their median risk score.The predictive efficiency of the immune gene prognosis model was evaluated by Kaplan-Meier analysis and Receiver Operating Characteristic(ROC)curve,and the correlation between immune gene prognostic risk model and the immune cell infiltration was analyzed.Results A total of 220 differentially expressed immune genes existed in Tumor group and Normal group.By Cox univariate and multivariate regression analysis,seven prognosis-related immune genes were screened,i.e.CXCL5(C-X-C motif Chemokine Ligand 5),IGHV5-51(Immunoglobulin Heavy Variable 5-51),IGKV1-33(Immunoglobulin Kappa Variable 1-33),CHGA(Chromogranin A),UCN(Urocortin),VIP(Vasoactive Intestinal Peptide)and NR3C2(Nuclear Receptor subfamily 3 group C member 2).The overall survival rate of COAD patients was higher in low-risk group than in high-risk group(P<0.001).The overall 5-year survival rate in high-risk group and low-risk group were 49.4% and 75.8%, respectively. ROC curve showed that AUCwas 0.741, suggesting that the immune gene prognosis model had a good predictive efficiency, and was associated with immune cellinfiltration of B cells, CD4+ T cells, CD8+ T cells, dendritic cells, macrophages and natural killer cells. Conclusions An immunege

关 键 词：结肠腺癌 免疫基因 癌症基因组图谱 预后 个体化诊疗 

分 类 号：R735.3[医药卫生—肿瘤]