基于多组学数据分析PUF家族基因在肝癌中的表达及其临床意义  

Analysis of the Expression and Clinical Significance of PUF Family Genes in Hepatocellular Carcinoma Based on Multi-omics Data

作　　者：唐超峰[1] 柳科军 陈本栋[1] 卜阳 TANG Chaofeng;LIU Kejun;CHEN Bendong;BU Yang(Department of Hepatobiliary Surgery,the General Hospital of Ningxia Medical University,Yinchuan 750004,China;Department of Hepatobiliary Surgery,People’s Hospital of Ningxia Hui Autonomous Region,Yinchuan 750002,China)

机构地区：[1]宁夏医科大学总医院肝胆外科,银川750004 [2]宁夏回族自治区人民医院肝胆外科,银川750002

出　　处：《宁夏医科大学学报》2023年第7期668-675,共8页Journal of Ningxia Medical University

基　　金：国家自然科学基金项目(81960533)。

摘　　要：目的 探讨PUF家族基因(PUM1、PUM2、PUM3)作为肝癌的潜在预后标志物及其可能的分子调控机制。方法 TCGA数据库分析PUM1、PUM2、PUM3在正常肝组织、癌旁组织和肝癌组织中的表达及差异;Kaplan-Meier曲线分析PUM1、PUM2、PUM3表达与肿瘤患者预后;c Bio Portal数据库分析PUM1、PUM2、PUM3在肝癌中的突变情况;String网站及Cytoscape软件构建PUM1、PUM2、PUM3共表达基因的蛋白互作网络;GO/KEGG对PUM1、PUM2、PUM3共表达基因进行功能富集分析;TIMER 2.0数据库分析PUM1、PUM2、PUM3与肿瘤免疫细胞浸润的相关性。结果 PUM1、PUM2、PUM3在肝癌组织的表达高于癌旁组织及正常肝组织(P均<0.001);PUM1、PUM2、PUM3阳性蛋白表达主要集中于细胞核或细胞质;PUM1表达与患者年龄、BMI及组织学分级相关(P均<0.05);PUM2表达与患者性别、年龄及病理分期相关(P均<0.05);PUM3表达与肿瘤T分期及病理分期相关(P均<0.05);PUM1、PUM2、PUM3高表达的肝癌患者预后差(P<0.05);PUMs共表达基因主要富集于RNA剪切、P53类介质对信号转导的正向调节作用、剪接体组装、转录因子复合体、钙粘蛋白(Ecadherin)结合、P53结合位点及细胞周期等通路。同时PUM1、PUM2、PUM3表达与辅助性T细胞、中枢记忆性T细胞、辅助性T细胞2及嗜酸性粒细胞浸润水平呈正相关关系。结论 PUM1、PUM2、PUM3在肝癌发生发展过程中发挥重要作用,可作为潜在的分子治疗靶点和预后评价标志物。Objective To explore PUF family genes(PUM1、PUM2、PUM3)as potential prognostic markers for hepatocellular carcinoma(HCC)and their possible molecular regulatory mechanisms.Methods The expression of PUM1、PUM2、PUM3 in normal liver tissue,precancerous tissues,and HCC tissues were analyzed using the TCGA database.Kaplan-Meier curves were used to analysis the association of PUM1、PUM2、PUM3 expression with the prognosis of HCC patients.The cBioPortal database was used to study the PUM1、PUM2、PUM3 mutation in HCC.The protein interaction layout was created by Cytoscape software and String.All the co-expressed with PUM1、PUM2、PUM3 in HCC were subjected to enrichment analysis of GO functions and KEGG pathways.The tumor immune estimation resource(TIMER)database was used for differential analysis of PUM1、PUM2、PUM3 and immune infiltrates in HCC.Results The expression of PUM1、PUM2、PUM3 in HCC tissue was statistically significantly higher than that in paraneoplastic tissue and normal liver tissue(P all<0.001).PUM1、PUM2、PUM3 proteins expression were mainly found in the cytoplasm and nucleus.PUM1 expression was significantly correlated with patient age,BMI and histological grade(P all<0.05).PUM2 expression was correlated with patient gender,age and pathological stage(P all<0.05).PUM3 expression was correlated with tumor T stage and pathological stage(P all<0.05).High PUM1、PUM2、PUM3 expression correlated with poor prognosis of HCC patients(P<0.05).The co-expressed genes were mainly enriched in RNA splicing,signal transduction by P53 class mediator,spliceosome complex,transcription factor complex,E-cadherin binding,P53 binding and cell cycle.Besides,the expression of PUM1、PUM2、PUM3 were positively correlated with infiltration of helper T cells,central memory helper T cells,T helper 2 cells,and eosinophils.Conclusion PUM1、PUM2、PUM3 might play important roles in the onset and progression of HCC,and might provide potential molecular therapeutic targets and prognostic biomarkers for this prevalent

关 键 词：肝细胞癌 PUF家族基因 预后 免疫浸润 生物信息学 

分 类 号：R735.7[医药卫生—肿瘤]