植物同源结构域锌指蛋白5A在肝细胞癌中的表达及其临床意义  

Expression and clinical significance of plant homeodomain finger protein 5A in hepatocellular carcinoma

作　　者：谢昌明 张维志 Xie Changming;Zhang Weizhi(Department of Thyroid Surgery,the First Affiliated Hospital of Harbin Medical University,Harbin 150001,China;Department of Liver Surgery,the First Affiliated Hospital of Harbin Medical University,Harbin 150001,China)

机构地区：[1]哈尔滨医科大学附属第一医院甲状腺外科,哈尔滨150001 [2]哈尔滨医科大学附属第一医院肝脏外科,哈尔滨150001

出　　处：《中华实验外科杂志》2023年第10期1947-1950,共4页Chinese Journal of Experimental Surgery

摘　　要：目的基于生物信息学方法分析植物同源结构域锌指蛋白5A(PHF5A)在肝细胞癌(肝癌)中的表达及临床意义。方法肿瘤免疫估计资源(TIMER)、UALCAN及临床蛋白质组学肿瘤分析联盟(CPTAC)数据库分析PHF5A在肝癌中的表达。UALCAN数据库分析PHF5A表达与肝癌临床病理学特征的相关性,并利用癌症基因组图谱(TCGA)肝癌数据进行二元Logistics回归验证。基因表达谱交互分析(GEPIA)、Kaplan-Meier Plotter数据库分析PHF5A表达与肝癌患者预后的相关性,通过Cox回归模型评估PHF5A的预后价值并构建列线图预测患者的预后。LinkedOmics数据库分析肝癌中PHF5A的共表达基因,并进行基因本体(GO)及京都基因和基因组百科全书(KEGG)富集分析,预测其生物学功能。基因集富集分析(GSEA)探讨PHF5A在肝癌中作用的机制。通过STRING数据库进一步构建PHF5A的蛋白质-蛋白质相互作用(PPI)网络。单样本基因集富集分析(ssGSEA)研究PHF5A表达与肿瘤免疫浸润的关系,TIMER数据库分析PHF5A与免疫检查点基因的相关性。两组PHF5A表达比较采用t检验或秩和检验,生存分析采用Kaplan-Meier法及Log-rank检验,采用Cox比例风险回归模型确定PHF5A对预后的价值。结果UALCAN数据库显示肝癌组织中PHF5A mRNA表达水平升高[癌比癌旁为23.761(18.367,30.691)比12.462(10.650,14.983),P<0.001]。CPTAC数据库进一步验证,肝癌中PHF5A蛋白表达量亦显著高于癌旁[0.006(-0.680,0.577)比-1.990(-2.582,-1.477),P<0.001]。PHF5A与肝癌患者临床分期(Ⅰ期比Ⅲ期)、组织学分级(G1比G3,G1比G4,G2比G3)显著正相关(P<0.05);Logistics回归分析显示,PHF5A与临床分期、组织学分级、T分期以及甲胎蛋白(AFP)水平显著相关[比值比(OR)=1.426、2.279、1.409、2.335,P<0.05]。GEPIA数据库显示PHF5A高表达组总生存期(OS)及无病生存期(DFS)更短[风险比(HR)=1.700,1.400,P<0.05];Kaplan-Meier Plotter数据库显示PHF5A高表达组OS、无进展生存期(PFS)�Objective To analyze the expression and clinical significance of plant homeodomain finger protein 5A(PHF5A)in hepatocellular carcinoma(HCC)based on bioinformatics.Methods Tumor immune estimation resource(TIMER),UALCAN and Clinical Proteomic Tumor Analysis Consortium(CPTAC)databases were used to analyze the expression of PHF5A in HCC.The correlation between PHF5A expression and clinicopathological characteristics of HCC patients was analyzed based on UALCAN database,and binary Logistics regression was performed using the cancer genome atlas(TCGA)HCC data to further analyze.The effect of PHF5A expression on the prognosis of HCC patients was analyzed based on Gene Expression Profling Interactive Analysis(GEPIA)and Kaplan-Meier Plotter databases.The prognostic value of PHF5A was further evaluated by Cox regression model and the nomogram model was further constructed to predict the prognosis of HCC patients.Co-expression genes of PHF5A in HCC were analyzed based on LinkedOmics database,and input into DAVID database for Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis to predict the biological function of PHF5A.Gene set enrichment analysis(GSEA)was used to explore the mechanism of PHF5A in HCC.The protein-protein interaction(PPI)network of PHF5A was further constructed by STRING database.Single sample gene set enrichment analysis(ssGSEA)was used to investigate the relationship between PHF5A expression and tumor infiltration immune cells.TIMER was used to analyze the correlation between PHF5A expression and immune checkpoint genes.The comparison of PHF5A expression between two groups was performed using t-test or Mann-Whitney U test.Survival analysis was conducted using the Kaplan-Meier method and assessed with the Log-rank test.Cox proportional hazard regression model was used to determine the prognostic value of PHF5A.Results UALCAN database showed that PHF5A mRNA expression level was up-regulated in HCC[23.761(18.367,30.691)vs.12.462(10.650,14.983),P<0.001].Further validation from

关 键 词：肝细胞癌 植物同源结构域锌指蛋白5A 预后 生物信息学 

分 类 号：R735.7[医药卫生—肿瘤]