生物信息学分析转录因子E2F1/2/7/8在前列腺癌中的作用

Bioinformatics analysis of E2F1/2/7/8 transcription factors in prostate cancer

目的通过生物信息学分析转录因子E2F1/2/7/8在前列腺癌(PCa)中的生物学作用。方法在GEPIA数据库中,以50%为界值将E2F1/2/7/8基因表达水平分为低表达组和高表达组,分析E2F1/2/7/8表达差异与PCa患者无病生存率(DFS)的关系。TCGA数据库包含497例PCa和52例正常前列腺组织,UALCAN网站分析TCGA数据库中基因转录水平及其与Gleason评分的关系。分别获取E2F1/2/7/8的相关基因,将4组相关基因取交集绘制韦恩图获得最终相关基因,进一步行GO功能分析和KEGG通路富集分析。结果E2F1/2/7/8表达水平越低,PCa患者DFS越高(均P<0.05)。与正常前列腺组织比较,PCa组织中E2F1/2/7表达升高(均P<0.05)。E2F1/2/7/8表达水平越高,PCa患者的Gleason评分越高(均P<0.05)。126个最终相关基因的GO功能分析显示,相关基因在生物学过程(BP)方面主要富集于细胞分裂、有丝分裂、姐妹染色体结合、细胞增殖以及DNA复制等,在细胞成分(CC)方面主要富集于细胞核、细胞核质、细胞质以及细胞溶质等,在分子功能(MF)方面主要富集于蛋白结合、ATP及DNA结合等;KEGG富集于细胞周期、卵母细胞减数分裂、孕酮介导的卵母细胞成熟等信号通路。结论转录因子家族中E2F1/2/7/8可通过调节细胞周期,发挥致癌基因作用。

Objective To investigate the biological role of E2F1/2/7/8 transcription factors in prostate cancer(PCa).Methods GEPIA database was used for survival analysis.The gene expression levels were divided into low expression group and high expression group according to 50%threshold,and the relationship between E2F1/2/7/8 expression levels and disease free survival(DFS)of PCa patients was analyzed.UALCAN database was used to analyze the transcription levels of E2F1/2/7/8 between 497 PCa and 52 normal prostate tissue in TCGA database,and the relationship between E2F1/2/7/8 and Gleason score.Genes related to E2F1/2/7/8 were screened respectively,and the GO function analysis and KEGG pathway enrichment analysis of the final related genes were performed by DAVID website.Results Survival analysis showed that the expression differences of E2F1/2/7/8 were correlated with disease-free survival(DFS)of PCa patients(all P<0.05).E2F1/2/7 were high expressed in PCa.In addition,the overexpression of E2F1/2/7/8 significantly matched more advanced Gleason score.Then 126 final related genes were screened out.GO function analysis revealed enrichment of these genes.In the case of biological process(BP),GO terms mainly included cell division,mitotic nuclear division,sister chromatid cohesion,cell proliferation,DNA replication.For the cellular component(CC),the GO terms principally included nucleus,nucleoplasm,cytoplasm and cytosol.For the molecular function(MF),the GO terms predominantly included protein binding,ATP binding and DNA binding.KEGG pathway analysis indicated that these genes were mainly enriched in cell cycle,oocyte meiosis and progesterone-mediated oocyte maturation signaling pathway.Conclusions E2F1/2/7/8 family can play an oncogene role by regulating cell cycle in PCa.