肝细胞癌组织核孔蛋白85(NUP85)高表达与免疫细胞浸润及预后相关性分析  

Analysis of correlation between high expression of nucleoporin 85(NUP85)and immune cell infiltration in hepatocellular carcinoma

作　　者：刘新宇 丁泽邦 吴焕 马俊杰 陆进 LIU Xinyu;DING Zebang;WU Huan;Ma Junjie;LU Jin(Clinical Medical College,College of Basic Medicine,Bengbu Medical University,Bengbu 233030,China;Mental Health College,College of Basic Medicine,Bengbu Medical University,Bengbu 233030,China;Department of Anatomy,College of Basic Medicine,Bengbu Medical University,Bengbu 233030,China)

机构地区：[1]蚌埠医科大学临床医学院,安徽蚌埠233030 [2]蚌埠医科大学精神卫生学院,安徽蚌埠233030 [3]蚌埠医科大学基础医学院人体解剖学教研室,安徽蚌埠233030

出　　处：《细胞与分子免疫学杂志》2024年第6期508-519,共12页Chinese Journal of Cellular and Molecular Immunology

基　　金：安徽省教育厅自然科学研究重点项目(2023AH051929);2021年教育部产学合作协同育人项目(202101160001)。

摘　　要：目的 探究核孔蛋白85(NUP85)在肝细胞癌(HCC)中的表达意义及免疫相关性分析。方法 综合利用多种在线数据库分析NUP85在HCC中的mRNA表达、蛋白表达以及突变情况,并进行预后诊断价值分析;采用单细胞测序数据及肿瘤免疫评估资源(TIMER)和基因表达谱交互作用分析2021(GEPIA2021)数据库分析NUP85的免疫相关性;利用基因组癌症分析(GSCA)和临床生信之家分析NUP85的药物敏感性;通过肝细胞癌综合分子数据库(HCCDB)筛选NUP85在HCC中的共表达基因,并利用R语言“limma包”分析NUP85及其相关基因的相关性;再利用R语言“clusterProfiler包”分析NUP85及其相关基因的基因本体论(GO)功能注释、京都基因与基因组百科全书(KEGG)以及基因集富集分析(GSEA);利用临床生信之家对NUP85及其相关基因进行列线图和预后风险评分模型的构建。结果 NUP85的mRNA和蛋白质在HCC中表达上调,在不同分期和分级均高表达,不利于患者预后;而其在HCC样本中突变率是19%,显著影响患者的总生存期(OS)、疾病特异性生存(DSS)以及无进展生存(PFS),且其在巨噬细胞、 B细胞、 T细胞等多种免疫细胞中高表达并与多种免疫细胞浸润水平呈正相关;此外,NUP85的表达与米尔达美替尼(PD0325901)、维莫非尼的结构类似物(PLX4720)和瑞法替尼(PD0325901)等多用药物具有显著相关性。NUP85及其共表达基因的GO功能主要富集在细胞器裂变、核分裂和染色体分离等,KEGG通路主要富集在细胞周期和运动蛋白等,并显著不利于HCC患者OS,且对HCC患者1年、 3年和5年OS预后诊断的ROC曲线下面积AUC均大于0.7。结论 NUP85高表达HCC患者预后差,并与多种免疫细胞和药物相关,可作为HCC诊断、治疗和预后的生物标志物。Objective To investigate the significance of nucleoporin 85(NUP85)ex-pression in hepatocellular carcinoma(HCC)and analyze its relevance to immune response.Methods A comprehensive analysis was conducted using various online databases to assess the mRNA and protein expression of NUP85 in HCC,as well as its mutation status and prognostic diagnostic value.The immune relevance of NUP85 was evaluated using single-cell sequencing data and resources from the Tumor Immune Estimation Resource(TIMER)and the Gene Expression Profiling Interactive Analysis 2021(GEPIA2021)databases.The drug sensitivity of NUP85 was analyzed through the Genomic Landscape of Cancer(GSCA)and the Clinical Bioinformatics Home.Co-expressed genes of NUP85 in HCC were filtered using the Hepatocellular Carcinoma Comprehensive Molecular Database(HCCDB),and the correlation between NUP85 and its related genes was analyzed using the R language“limma”package.The gene ontology(GO)functions,Kyoto Encyclopedia of Genes and Genomes(KEGG),and Gene Set Enrichment Analysis(GSEA)of NUP85 and its related genes were performed using the R language“clusterProfiler”package.The Clinical Bioinformatics Home was utilized to construct heatmaps and prognostic risk scoring models for NUP85 and its related genes.Results NUP85 mRNA and protein expression were upregulated in HCC,showing high levels across dif-ferent stages and grades,which indicates a poor prognosis for patients.The mutation rate of NUP85 in HCC samples was 19%,significantly affecting the overall survival(OS),disease-specific survival(DSS),and progression-free survival(PFS)of patients.NUP85 was highly expressed in various immune cells,including macrophages,B cells,and T cells,and was positively correlated with the infiltration levels of multiple immune cells.The expression of NUP85 was significantly correlated with multiple drugs,such as Milademetan(PD0325901),a structural analog of Vemurafenib(PLX4720),and Regorafenib(PD0325901).The GO functions of NUP85 and its co-expressed genes were mainly enriched in

关 键 词：核孔蛋白85(NUP85) 肝细胞癌 单细胞分析 免疫浸润 生物信息学 

分 类 号：Q279[生物学—细胞生物学] R392.12[医药卫生—免疫学] R735.7[医药卫生—基础医学] Q811.4