肝细胞癌中免疫相关基因的预后作用  

Prognostic Role of Immune-related Genes in Hepatocellular Carcinoma

作　　者：王珏 金宗睿 王维[1] 易麒麟 王继龙 朱海[1] 徐邦浩[1] 郭雅[1] 文张[1] WANG Jue;JIN Zongrui;WANG Wei;YI Qilin;WANG Jilong;ZHU Hai;XU Banghao;GUO Ya;WEN Zhang(Department of Hepatobiliary Surgery,The First Affiliated Hospital of Guangxi Medical University,Nanning 530021,China)

机构地区：[1]广西医科大学第一附属医院肝胆外科,南宁530021

出　　处：《肿瘤防治研究》2022年第6期599-605,共7页Cancer Research on Prevention and Treatment

基　　金：国家自然科学基金青年科学基金(81902983);国家自然科学基金地区科学基金(81560387);广西自然科学基金(2018JJB140382);广西医科大学第一附属医院“优秀医学英才”科研创新能力培养项目资助(180327);广西医疗卫生适宜技术开发与推广应用项目(S2018100)。

摘　　要：目的探讨肝细胞癌(HCC)患者免疫相关基因特征的潜在预后生物标志物。方法从TCGA数据库下载原始肝细胞癌数据,执行单样本基因集富集分析计算每个样本的免疫活性。利用“GSVA”包和“hclust”包将HCC样本分成高和低免疫细胞浸润组。ESTIMATE算法对每个HCC样本中的肿瘤微环境进行评分。“limma”包和维恩图确定有效的免疫相关基因。单因素Cox、LASSO回归和多因素Cox回归分析探索关键基因。“rms”包建立列线图并绘制校准曲线。结果与高免疫细胞浸润组相比,低免疫细胞浸润组中样本的肿瘤纯度更高,免疫评分、ESTIMATE评分和基质评分较低。高免疫细胞浸润组免疫成分更丰富,TIGIT、PD-L1、PD-1、LAG3、TIM-3、CTLA4和HLA家族的表达水平更高。多因素Cox回归分析显示4个免疫相关基因(S100A9、HMOX1、IL18RAP和FCER1G)被用来构建预后模型。与其他临床特征相比,该预后模型的风险评分被确认为独立的预后因素。结论本研究确定了肝细胞癌免疫相关核心基因,可用于肝细胞癌的靶向治疗和免疫治疗。Objective To identify the potential prognostic biomarkers of the immune-related genes signature for patients with hepatocellular carcinoma(HCC).Methods Original HCC data were downloaded from TCGA,and the immune activity of each sample was calculated by ssGSEA.HCC samples were divided into high and low immune cell infiltration groups by“GSVA”package and“hclust”package.The ESTIMATE algorithm scored the tumor microenvironment in each HCC sample.The“limma”package and Venn diagram identified effective immune-related genes.Univariate Cox,Lasso regression and multivariate Cox regression analyses were used to explore key genes.The“rms”package was used to create nomograms and draw calibration curves.Results Compared with the high immune cell infiltration group,the tumor purity of the samples in the low immune cell infiltration group was higher,the immune score,ESTIMATE score and stromal score were lower.In the high immune cell infiltration group,the immune components were more abundant,and the expression levels of TIGIT,PD-L1,PD-1,LAG3,TIM-3,CTLA4 and HLA family were higher.Multivariate Cox regression analysis showed that four immune-related genes(S100A9,HMOX1,IL18RAP and FCER1G)were used to construct the prognosis model.Compared with other clinical features,the risk score of this prognostic model was recognized as an independent prognostic factor.Conclusion This study identified the immune-related core genes which may be used in targeted therapy and immunotherapy of HCC.

关 键 词：肝细胞癌 TCGA数据库 免疫基因 预后 

分 类 号：R735.7[医药卫生—肿瘤]