引用本文:祖 玲,李万里,刘天奇.eIF4E3与肝细胞癌患者预后的关联性及其作用机制分析[J].中国临床新医学,2023,16(6):601-608.
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eIF4E3与肝细胞癌患者预后的关联性及其作用机制分析
祖 玲,李万里,刘天奇
530200 南宁,广西中医药大学研究生院(祖 玲,李万里);530021 南宁,广西壮族自治区江滨医院普通外科(刘天奇)
摘要:
[摘要] 目的 分析真核翻译起始因子4E家族成员3(eIF4E3)与肝细胞癌(HCC)患者预后的关联性及其作用机制。方法 通过肿瘤免疫评估资源(TIMER)数据库、癌症基因集分析(GSCA)数据库、肝细胞癌整合分子数据库(HCCDB)以及UALCAN数据库分析eIF4E3在HCC和正常肝组织中的表达差异。应用UALCAN数据库分析eIF4E3的转录水平与HCC患者临床病理特征的关系。应用GSCA数据库和Kaplan-Meier Plotter数据库进行生存分析。应用Linked Omics数据库对eIF4E3的共表达基因进行探索,对其共表达基因作基因本体论(GO)分析和京都基因与基因组百科全书(KEGG)分析。通过肿瘤免疫相互作用数据库(TISIDB)和Sanger Box平台分析eIF4E3与肿瘤微环境中免疫浸润的关系。结果 HCC组织中eIF4E3的表达水平显著低于正常肝组织(P<0.05)。在HCC患者中,eIF4E3低表达组的总生存期(OS)、无病生存期(DFS)、无病进展生存期(PFS)和无疾病间隔(DFI)均较eIF4E3高表达组显著缩短(P<0.05)。功能富集分析结果显示,eIF4E3的功能主要富集于细胞黏附、细胞周期以及免疫反应(P<0.05)。eIF4E3表达水平与初始CD4+ T细胞、静息自然杀伤(NK)细胞、单核细胞、静息肥大细胞及嗜酸性粒细胞的浸润丰度呈显著负相关(P<0.05),与静息CD4记忆T细胞、活化CD4记忆T细胞、M1巨噬细胞、活化树突状细胞、静息树突状细胞及中性粒细胞浸润丰度呈正相关(P<0.05)。结论 eIF4E3是一种潜在的抑癌基因,可能通过影响HCC肿瘤微环境的免疫浸润状态来影响患者预后,有作为HCC免疫治疗靶点的应用前景。
关键词:  真核翻译起始因子4E家族成员3  预后  免疫浸润  肝细胞癌  肿瘤微环境
DOI:10.3969/j.issn.1674-3806.2023.06.14
分类号:R 735.7
基金项目:广西卫生健康委科研项目(编号:Z20180722)
Analysis of the correlation between eIF4E3 and the prognosis of hepatocellular carcinoma patients and exploration of its mechanisms of action
ZU Ling, LI Wan-li, LIU Tian-qi
Graduate School of Guangxi University of Chinese Medicine, Nanning 530200, China
Abstract:
[Abstract] Objective To analyse the correlation between eukaryotic translation initiation factor 4E family member 3(eIF4E3) and the prognosis of hepatocellular carcinoma(HCC) patients and to explore its mechanisms of action. Methods The expression differences of eIF4E3 in HCC and normal liver tissues were analyzed by using Tumor Immune Estimate Resource(TIMER) database, Gene Set Cancer Analysis(GSCA) database, Hepatocellular Carcinoma Database(HCCDB) and University of Alabama at Birmingham Cancer Data Analysis Portal(UALCAN) database, and the relationship between the transcription level of eIF4E3 and the clinicopathological characteristics of HCC patients was analyzed by using UALCAN database. The GSCA database and Kaplan-Meier Plotter database were used for survival analysis. The Linked Omics database was used to explore the co-expression genes of eIF4E3, and the co-expressed genes were analyzed by using Gene Ontology(GO) and the Kyoto Encyclopedia of Genes and Genomes(KEGG). Finally, the Tumor-Immune System Interactions Database(TISIDB) and the Sanger Box platform were used to analyze the relationship between eIF4E3 and immune invasion in the tumor microenvironment. Results The expression level of eIF4E3 in the HCC tissues was significantly lower than that in the normal liver tissues(P<0.05). In the HCC patients, the overall survival(OS), disease-free survival(DFS), progression-free survival(PFS) and disease-free interval(DFI) in the low eIF4E3 expression group were significantly shorter than those in the high eIF4E3 expression group(P<0.05). The results of functional enrichment analysis showed that the function of eIF4E3 was mainly enriched in cell adhesion, cell cycle and immune response(P<0.05). The expression level of eIF4E3 was significantly negatively correlated with the infiltration abundances of naive CD4+ T cells, resting natural killer(NK) cells, monocytes, resting mast cells and eosinophils(P<0.05), and positively correlated with the infiltration abundances of resting CD4 memory T cells, activated CD4 memory T cells, M1 macrophages, activated dendritic cells, resting dendritic cells and neutrophils(P<0.05). Conclusion eIF4E3 is a potential tumor suppressor gene, which may affect the prognosis of patients by affecting the immune invasion status in the HCC tumor microenvironment, and has the application prospect as a target of HCC immunotherapy.
Key words:  Eukaryotic translation initiation factor 4E family member 3(eIF4E3)  Prognosis  Immune infiltration  Hepatocellular carcinoma  Tumor microenvironment