基于相对表达量基因对方法筛选乙肝病毒相关性肝癌免疫预后标志物  

Screening of immune prognostic markers of hepatitis B virus-related liver cancer based on relative gene expression level

作　　者：陈颍 李淼新 李萌萌 曹素梅[1] CHEN Ying;LI Miao-xin;LI Meng-meng;CAO Su-mei(Department of Cancer Prevention,Sun Yat-sen University Cancer Center,Guangzhou,Guangdong 510080;Zhongshan School of Medicine,Sun Yat-sen University,Guangzhou,Guangdong 510080,China)

机构地区：[1]中山大学肿瘤防治中心肿瘤预防研究科,广东广州510080 [2]中山大学中山医学院,广东广州510080

出　　处：《热带医学杂志》2021年第11期1379-1383,1388,共6页Journal of Tropical Medicine

基　　金：国家重点研发计划(2017YFC0907102)。

摘　　要：目的探索乙肝病毒(HBV)相关性肝癌的预后免疫基因对标志物,为乙肝相关性肝癌患者的监测与预后治疗提供依据。方法应用生物信息学研究方法,将基因表达谱数据库(GEO)与癌症基因组图谱(TCGA)数据库的肝癌转录组数据集、临床信息和来自免疫分析(ImmPort)数据库的免疫相关基因集进行整合,通过随机生存森林与比例风险回归模型(Cox)回归方法在GEO数据集上建立预测模型,识别与乙肝病毒相关性肝癌的免疫基因对标志物,并用TCGA数据集进行验证,以AUC为指标评价模型预测能力,运用Metascape进行基因功能富集与疾病关联分析。结果构建了乙肝病毒相关肝癌的7-免疫基因对预后标志物,生存分析(K-M)显示该标志物在两个数据集中均能显著区分开乙肝病毒相关肝癌高低风险值的患者,其5年生存率预测曲线下面积(AUC)值分别为0.755和0.844,与15-基因预后标志物5年内生存率预测AUC值分别为0.630和0.814相比,具有更好的预测准确度。基因功能富集分析与疾病关联分析显示免疫基因对标志物与病毒反应以及肝脏功能失调等疾病具有重要联系。结论 7-免疫基因对标志物在乙肝病毒相关肝癌患者中具有潜在的预后预测价值,可为后续的深入探索与诊疗提供线索。Objective To screen of immune prognostic markers of hepatitis B virus(HBV)-related liver cancer based on relative gene expression level,and provid guidance and clue for clinical practice.Methods Transcriptome profiles,clinical characteristics and immune-related gene sets were downloaded and curated from gene expression omnibus(GEO),the cancer genome atlas(TCGA) and the immunology database and analysis portal(ImmPort).An integrated analysis workflow was designed to construct a predictive model by performing Random Survival Forest and proportional hazards model(Cox)regression method.The AUC was used to evaluate the accuracy of the model.Finally,a website-based tool Metascape was used to conduct biological enrichment analysis of the prognostic markers.Results 7 immune-related prognostic genepair signatures of HBV-related HCC were identified.Kaplan-meier(K-M)analysis indicated the prognostic biomarkers could discriminate the high-risk patients from low-risk patients.Furthermore,compared with 15-gene prognostic markers that achieved area under curve(AUC)values of 0.630 and 0.814,our markers obtained a better predictive power with AUC values of 0.755 and 0.844 for predicting a 5-year overall survival rate,respectively.The integrated functional analysis suggested that our biomarkers had an important prognostic value associated with pathology signals like virus response and liver functional disorder.Conclusion The 7 immune-related gene-pair biomarkers had potential prognostic value for HBVrelated HCC patients,and might shed light on further study a clinical treatment.

关 键 词：生物信息学 乙肝病毒 肝细胞癌 基因对 标志物 

分 类 号：R735.7[医药卫生—肿瘤]