肝细胞癌组织中RNF216的表达及临床意义

Expression and clinical significance of RNF216 in hepatocellular carcinoma tissues

目的探讨肝细胞癌(HCC)组织中环指蛋白216(RNF216)的表达及临床意义。方法从肿瘤基因表达图谱(TCGA)数据集中下载HCC患者的基因表达和临床特征数据,分析RNF216表达与HCC临床病理特征和预后的关系;进一步采用Kaplan-Meier Plottor在线数据库对HCC组织RNF216 mRNA表达与预后的关系进行大数据分析。应用基因本体(GO)分析联合京都基因和基因组百科全书(KEGG)功能富集分析筛选RNF216可能参与并主要影响的生物学功能或通路。结果RNF216表达与临床分期、T分期、M分期和总生存期有关(P<0.05),而与年龄、N分期、手术方式和放疗无关(P>0.05)。Kaplan-Meier Plottor在线预后分析显示,RNF216高表达与较短的无复发生存期(HR=1.52,95%CI:1.09~2.11)、无进展生存期(HR=1.51,95%CI:1.12~2.02)、疾病特异性生存期(HR=1.95,95%CI:1.21~3.16)和总生存期(HR=1.79,95%CI:1.23~2.61)均有关(P<0.05)。以Spearman相关系数≥0.5为关联明显标准筛选RNF216高度关联基因13个:FOXK1、ANKRD52、CCDC93、TNRC18、C7orf70、RNF216L、HEATR2、USP42、POM121C、KCTD7、FBXL18、MED12和ZMYM3。GO分析发现,RNF216及共表达基因主要为细胞膜和胞核成分,大多与蛋白、离子和核酸结合,具有催化活性和转移酶活性,参与各种生物学调控和代谢过程。RNF216高表达样本富集至Hedgehog、Notch、ErbB和Wnt信号通路等基因集。结论HCC组织中RNF216表达与多个临床病理特征有关,且RNF216表达在HCC中是一个预后不良因素,可作为潜在评估HCC预后的分子标志物。

Objective To investigate the expression of ring finger protein 216(RNF216)in hepatocellular carcinoma(HCC)tissues and its relationship with clinical significance.Methods Data of gene expression and clinical characteristics of HCC patients were downloaded from the Cancer Genome Atlas(TCGA).The relationship between RNF216 expression and clinicopathological characteristics and prognosis of HCC was analyzed.The relationship between RNF216 expression and prognosis of HCC patients was further analyzed using Kaplan-Meier Plottor online database.Using gene ontology(GO)analysis and functional enrichment analysis of Kyoto Encyclopedia of Genes and Genomes(KEGG),we screened the biological functions or pathways that RNF216 may participate in and mainly influence.Results The expression of RNF216 was related to clinical stage,T stage,M stage and overall survival(P<0.05),but not with age,N stage,surgical method and radiotherapy(P>0.05).The online prognostic analysis of Kaplan-Meier Plottor showed that the high-expression of RNF216 was associated with shorter relapse-free survival(HR=1.52,95%CI:1.09-2.11),progression-free survival(HR=1.51,95%CI:1.12-2.02),disease-specific survival(HR=1.95,95%CI:1.21-3.16)and overall survival(HR=1.79,95%CI:1.23-2.61)with statistical significance(P<0.05).Thirteen highly associated genes of RNF216 were screened with Spearman correlation coefficient>0.5 as a significant criterion:FOXK1,ANKRD52,CCDC93,TNRC18,C7orf70,RNF216L,HEATR2,USP42,POM121C,KCTD7,FBXL18,MED12 and ZMYM3.Further GO analysis revealed that RNF216 and its co-expressed genes were mainly components of cell membrane and nucleus,mostly binding to proteins,ions and nucleic acids,having catalytic activity and transferase activity,and involved in various biological regulation and metabolic processes.RNF216 high-expression samples were enriched to Hedgehog,Notch,ErbB and Wnt signaling pathway gene sets.Conclusion The expression of RNF216 in HCC tissues is related to many clinicopathological features,and RNF216 expression is a bad prognostic factor in HCC,which can be used as a potential molecular marker for evaluating the prognosis of HCC.