实用肿瘤杂志2024，Vol.39Issue(6)：549-560,12.DOI:10.13267/j.cnki.syzlzz.2024.081
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
摘要
Abstract
Objective To explore the characteristic relationship between autophagy and hepatocellular carcinoma(HCC)in Asian popu-lation 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 regres-sion 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 iden-tified 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).Uni-variate and multivariate Cox analysis showed that ARG risk score and TNM stage were correlated with the overall survival of HCC patients(both P<0.01).The nomogram based on the ARG risk score and TNM stage had excellent performance for predicting the 1-,3-,and 5-year overall survival of HCC patients.Immunoinfiltration analysis showed that,compared with the low-risk group,the high-risk group had high-er levels of most innate and adaptive immune cell infiltration(all P<0.05).Gene Ontology(GO)analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis showed that the up-regulated genes in the high-risk group were mainly enriched in the pathways of leuko-cyte migration,cell motility and differentiation(all P<0.05).The analysis of differences in genomic alterations showed that patients in the high-risk group had a higher frequency of tumor protein p53(TP53)mutations(P=0.003),and patients in the low-risk group had a higher rate of lysine methyltransferase 2D(KMT2D)mutations(P=0.031).Conclusions This study established and validated the ARG-based risk score model which provided a practical reference index for predicting the prognosis of Asian HCC patients.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Key words
hepatocellular carcinoma/autophagy-related gene/Asian/prognostic risk model/nomogram/bioinformatics引用本文复制引用
陈睿鹏,臧洪婧,龙伟..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[J].实用肿瘤杂志,2024,39(6):549-560,12.基金项目
国家自然科学基金青年项目(82102805) （82102805）
湖南省自然科学基金项目(2021JJ40890) （2021JJ40890）
