基于生物信息学分析CENPN在肝癌中的预后价值和作用机制  

Prognostic value and mechanism of CENPN in liver hepatocellular carcinoma based on bioinformatics analysis

作　　者：周艳琳 刘俊 李勇莉 李林玉 赵冰(指导)[3] ZHOU Yanlin;LIU Jun;LI Yongli;LI Linyu;ZHAO Bing(Sanquan College of Xinxiang Medical University,Xinxiang 453003,China)

机构地区：[1]新乡医学院三全学院,新乡453003 [2]汕头大学医学院附属粤北人民医院医学研究中心,韶关512025 [3]郑州大学第三附属医院,郑州450001

出　　处：《中国免疫学杂志》2022年第13期1590-1596,共7页Chinese Journal of Immunology

基　　金：河南省科技攻关项目(192102310333,212102310770);河南省高校科技创新人才支持计划项目(18HASTIT045);河南省医学科技攻关计划联合共建项目(2018020385);河南省高等学校重点科研项目(21A310018);河南省医学教育研究项目(Wjlx2020319);河南省高校人文社会科学研究一般项目(2023-ZDJH-101)资助。

摘　　要：目的:基于生物信息学方法分析着丝粒蛋白N(CENPN)在肝细胞癌(LIHC)中的表达及预后价值,并预测其调控LIHC的可能机制。方法:基于TIMER2.0和GEPIA2数据库分析CENPN在TCGA LIHC组织中的表达。基于GEPIA2数据库,通过Cox和Logistic方法分析CENPN表达与LIHC患者病理分期和预后的关系。基于LinkedOmics数据库,通过Spearman方法分析CENPN在TCGA-LIHC中的共表达基因。基于DAVID数据库对Top 500差异性共表达基因进行GO功能和KEGG通路富集分析,并在KEGG网站中可视化细胞周期通路。基于cBioPortal数据库,通过Spearman和Pearson方法分析CENPN表达与甲基化的关系。基于TIMER数据库,通过Spearman方法分析CENPN表达与6种肿瘤浸润免疫细胞的关系。结果:CENPN在LIHC组织中的表达显著高于正常组织。此外,随着肿瘤分期进展,CENPN表达明显增多,在LIHC患者中,CENPN高表达患者总体生存期明显低于低表达患者,CENPN高表达患者无病生存期明显低于低表达患者。与CENPN表达存在相互作用的差异表达基因有TK1、C16orf61、KARS、COX4NB、COG4等,其主要富集于细胞裂解、蛋白质结合、细胞周期等生物过程。LIHC中CENPN的高表达与甲基化有关。CENPN的表达与6种肿瘤免疫细胞变化均相关。结论:CENPN可作为LIHC预后不良的标志物,其在LIHC中的高表达与甲基化有关,可能通过细胞周期和影响免疫细胞浸润相关通路调控LIHC的发生与发展。Objective:To analyze expression and prognosis of centromere protein N(CENPN)in liver hepatocellular carcinoma(LIHC)based on bioinformatics,and to predict possible mechanism of its regulation of LIHC.Methods:Expression of CENPN in TCGA LIHC was analyzed based on TIMER2.0 and GEPIA2 database.Relationship between CENPN expression and pathological stage and prognosis of patients in LIHC were analyzed by Cox and Logistic based on GEPIA database.Co-expression genes of CENPN in TCGA-LIHC was analyzed by Spearman based on LinkedOmics database.GO and KEGG enrichment in Top 500 co-expression genes were analyzed based on DAVID database.Cell cycle pathway was visualized in KEGG website.Relationship between CENPN expression and methylation level were calculated by Spearman and Pearson based on cBioPortal database.Correlation between CENPN expression and 6 tumor infiltrating immune cells was analyzed by Spearman based on TIMER database.Results:Expression of CENPN in LIHC tissues was significantly higher than that in normal tissues.Expression of CENPN was increased with progression of tumor stage.Overall survival rate of CENPN high expression patients was significantly lower than that in low expression patients.Disease-free survival rate of CENPN high expression patients was significantly lower than that in low expression patients.TK1,C16orf61,KARS,COX4NB,COG4 and other proteins were screened in differential expression of genes interacting with CENPN expression,which mainly enriched in biological processes such as cell division,protein binding and cell cycle.High expression of CENPN in LIHC was associated with methylation.Expression of CENPN was associated with all 6 tumor immune cells.Conclusion:CENPN can serve as a marker of poor prognosis in LIHC.High expression of CENPN in LIHC is associated with methylation.It may regulate occurrence and development of LIHC by cell cycle and tumor immune infiltration.

关 键 词：肝细胞癌 着丝粒蛋白N 预后标志物 细胞周期 肿瘤免疫 

分 类 号：R735.7[医药卫生—肿瘤]