原发性肝癌TEFM基因表达及临床意义数据挖掘分析

Expression and significance of TEFM gene in hepatocellular carcinoma were analyzed based on data mining

目的利用癌症基因图谱(TCGA)数据评估分析人线粒体转录延伸因子(TEFM)基因在原发性肝癌中的表达及临床意义,为原发性肝癌的诊治提供新思路。方法从TCGA中下载肝癌数据集,获得TEFM基因表达谱和临床数据;利用R语言及Perl语言对数据进行整理分析,比较肝癌组织及癌旁组织中TEFM表达量差异,并分析表达量与患者生存时间的关联性;通过Wilcoxon检验、Kruskal-Wallis检验及logistic回归进行临床关联性分析;利用基因富集化分析及蛋白相互作用网络分析TEFM可能参与的信号通路及潜在靶基因。结果与正常肝组织相比,TEFM基因在肝癌组织中高表达(FPKM=424,W=3591.00,P<0.05);TEFM基因高表达患者的5年生存率较低(χ^(2)=32.243,DF=1,P<0.05);TEFM基因表达量与临床病理分级(χ^(2)=19.082,DF=3,P<0.05)、病理分期(χ^(2)=13.373,DF=3,P<0.05)、肿瘤原发灶情况(χ^(2)=10.276,DF=3,P<0.05)关联;TEFM基因可以作为原发性肝癌独立预后因子(P<0.01);与TEFM基因编码蛋白相互作用的蛋白有POLRMT、TFB2M、MTERF1、MRPL21、ATAD5、TRMT10C、ADAP2、RAB11FIP4和CRLF3等;TEFM高表达样本富集到细胞周期、碱基修复、转录、RNA降解等相关基因集。结论TEFM可作为一种促癌基因,调控线粒体基因组转录,参与肝细胞癌的发生发展,有望为肝细胞癌的诊断与治疗提供新的靶点。

Objective The cancer genome atlas(TCGA)database was adopted in this paper to evaluate the expression and clinical significance of mitochondrial transcription elongation factor(TEFM)gene in primary liver cancer,with a view to providing new ideas for the diagnosis and treatment of primary liver cancer.Methods Liver cancer data set were downloaded from TCGA to obtain TEFM gene transcriptome profiling and clinical information data.R language and Perl language were used for statistical analysis,so as to compare the difference of TEFM expression in liver cancer tissues and adjacent tissues,and to analyze the difference of patients’survival time caused by the expression of different TEFM genes.Analysis of clinical correlation was carried out though Wilcoxon test、Kruskal-Wallis test and logistic regression.The key target genes and possible involvement pathways of TEFM were obtained by gene enrichment analysis and protein interaction network.Results Compared with normal liver tissue,TEFM gene was highly expressed in liver cancer tissue,thereby the difference was statistically significant(FPKM=424,W=3591.00,P<0.05).In addition,the 5-year survival rate of patients with high TEFM gene expression was significantly lower than that of patients with low TEFM gene expression(χ^(2)=32.243,DF=1,P<0.05).The expression of TEFM gene was significantly correlated with clinical pathological grade(G)(χ^(2)=19.082,DF=3,P<0.05),pathological stage(χ^(2)=13.373,DF=3,P<0.05)and primary tumor condition(T)(χ^(2)=10.276,DF=3,P<0.05).TEFMgene can be adopted as an independent prognostic factor for hepatocellular carcinoma(P<0.05).The proteins interacting with TEFM gene coding proteins included POLRMT,TFB2 M,MTERF1,MRPL21,ATAD5,TRMT10 C,ADAP2,RAB11 FIP4,CRLF3,etc.As indicated in GSEA enrichment analysis,TEFM high-expression samples were enriched to cell cycle,base repair,transcription,RNA degradation and other related gene sets.Conclusion As TEFMcan involve in the occurrence and development of hepatocellular carcinoma as a pro-oncogene,it is expected to provide a new target for the diagnosis and treatment of hepatocellular carcinoma.