基于公共数据库RNA-seq 鉴定亚洲人种肝细胞癌自噬相关基因预后特征  

Identification of prognostic signature of autophagy-related genes in Asian patients with hepatocellular carcinoma based on RNA-seq in public databases

作　　者：陈睿鹏 臧洪婧 龙伟 Chen Ruipeng;Zang Hongjing;Long Wei(Department of Pathology,Yueyang People's Hospital,Yueyang 414022,China;Department of Pathology,the Second Xiangya Hospital,Central South University,Changsha 410012,China;Department of Pathology,Liuyang Hospital of Traditional Chinese Medicine,Liuyang 410300,China)

机构地区：[1]岳阳市人民医院(湖南师范大学附属岳阳医院)病理科,湖南岳阳414022 [2]中南大学湘雅二医院病理科,湖南长沙410012 [3]湖南中医药大学附属第二中西医结合医院(浏阳市中医医院)病理科,湖南浏阳410300

出　　处：《实用肿瘤杂志》2024年第6期549-560,共12页Journal of Practical Oncology

基　　金：国家自然科学基金青年项目(82102805);湖南省自然科学基金项目(2021JJ40890)。

摘　　要：目的基于公共数据库探究亚洲人群肝细胞癌(hepatocellular carcinoma,HCC)与细胞自噬的特征关系。方法从PubMed上文献检索收集232个自噬相关基因(autuphagy-related genes,ARGs)。从癌症基因组图谱(The Cancer Genome Atlas,TCGA)和国际癌症基因组联盟(International Cancer Genome Consortium,ICGC)数据库分别纳入148例亚洲人种HCC样本(TCGA队列)和228例HCC样本(ICGC队列)。采用Kaplan-Meier法在TCGA队列中分析得到24个对HCC患者具有预后价值的ARGs。对TCGA队列采用聚类分析鉴定ARGs分子亚型。对TCGA队列应用LASSO-Cox回归方法建立基于ARGs的风险评分模型,采用ICGC队列作验证。采用单因素和多因素Cox回归分析筛选出具有统计学意义(P<0.01)的指标,用以构建包含ARGs风险评分和临床因素的列线图预测HCC患者的生存预后。采用受试者工作特征(receiver operating characteristic,ROC)曲线评估分析列线图的预测性能。分别采用WebGestalt数据库、TIMER数据库和相应R语言包在ARGs风险评分亚组中分析免疫浸润、富集途径和基因组改变状态。结果基于ARGs的HCC分子亚型[聚类A(Cluster-A)和聚类B(Cluster-B)]患者的总生存期比较,差异具有统计学意义(P<0.01)。使用LASSO-Cox回归方法筛选出特征性的5个预后相关ARGs[5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/inosine monophosphate cyclohydrolase(ATIC)、eukaryotic translation initiation factor 2 subunit alpha(EIF2S1)、histone deacetylase 1(HDAC1)、Rac family small GTPase 1(RAC1)和autophagy related 3(ATG3)]构建的风险评分模型将TCGA队列患者分为高风险组和低风险组。两组HCC患者总生存期比较,差异具有统计学意义(P<0.01)。单因素和多因素Cox分析显示,ARGs风险评分和TNM肿瘤分期与HCC患者总生存期相关(均P<0.01)。纳入ARGs风险评分和TNM肿瘤分期的列线图用于预测HCC患者1、3和5年总生存状态具有优秀的预测能力。免疫浸润分析显示,与低Objective To explore the characteristic relationship between autophagy and hepatocellular carcinoma(HCC)in Asian population based on public databases.Methods A total of 232 autophagy-related genes(ARGs)were collected by literature search.From The Cancer Genome Atlas(TCGA)and the International Cancer Genome Consortium(ICGC)databases,148 Asian HCC samples(TCGA cohort)and 228 HCC samples(ICGC cohort)were included.Kaplan-Meier method was used to screen 24 ARGs with prognostic value for HCC in the TCGA cohort.The molecular subtypes of ARGs were identified by cluster analysis in the TCGA cohort.The LASSO-Cox regression method was used to establish an ARG-based risk scoring model for the TCGA cohort,and the ICGC cohort was used for verification.Univariate and multivariate Cox analyses were used to select statistically significant indicators(P<0.01),which were used to construct a prognotic nomogram based on ARG risk score and clinical factors for HCC.The receiver operating characteristic(ROC)curve was used to evaluate the prediction performance of the nomogram.The WebGestalt and TIMER databases and corresponding R language packages were used to analyze immune infiltration,enrichment pathways,and genome alteration status in ARG risk score subgroups.Results The overall survival of HCC subtypes(Cluster-A and Cluster-B)based on ARGs was significantly different(P<0.01).Five prognostic ARGs were identified by LASSO-Cox regression,including 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/inosine monophosphate cyclohydrolase(ATIC),eukaryotic translation initiation factor 2 subunit alpha(EIF2S1),histone deacetylase 1(HDAC1),Rac family small GTPase 1(RAC1),and autophagy related 3(ATG3).A risk score model was constructed based on these five ARGs,and divided the TCGA cohort into high-and low-risk groups.The overall survival of HCC patients in these two groups was significantly different(P<0.01).Univariate and multivariate Cox analysis showed that ARG risk score and TNM stage were correlated with the overall survival

关 键 词：肝细胞癌 自噬相关基因 亚洲人种 预后风险模型 列线图 生物信息学 

分 类 号：R735.7[医药卫生—肿瘤]