基于公共数据库分析头颈部鳞癌中转录因子E2F家族表达及预后意义

Expression and prognostic significance of transcription factor E2F family in head and neck squamous cell carcinoma based on multiple public databases

目的通过生物信息学方法分析转录因子E2F家族(E2Fs)在头颈部鳞癌(HNSCC)中转录水平(mRNA)的表达,探究其在HNSCC发病中的作用。方法利用TCGA、GEPIA2和UALCAN公共数据库分析E2Fs mRNA在HNSCC中的表达及其与患者总生存期的关系,利用cBioPortal公共数据库筛选E2Fs的共表达基因构建共表达网络,通过R软件分析E2Fs及其共表达基因生物学功能。结果HNSCC中8个E2Fs的表达量显著高于癌旁组织,其中E2F4表达量最高,其次是E2F1、E2F6和E2F7。Spearman分析显示E2Fs成员间呈正相关性。基因本体论分析显示,E2Fs及其93个共表达基因主要通过DNA复制、细胞周期和范可尼贫血等信号通路,参与DNA复制和染色体分离等生物学过程。Cox单因素和多因素分析显示,E2F4(HR=1.502,95%CI:1.141~1.977)和E2F8(HR=0.698,95%CI:0.531~0.917)的高表达与HNSCC患者总生存期有关(P<0.05)。预后列线图显示E2F4高表达患者1年生存概率最低,其次是E2F8低表达患者。结论E2F家族在HNSCC中显著高表达,且E2F4和E2F8的表达水平与患者预后有关,E2Fs及其靶基因主要通过DNA复制、细胞周期和范可尼贫血等信号通路调控细胞染色体分离和DNA复制等生物学过程参与HNSCC的发生发展。

Objective To analyze the transcriptional expression of transcription factor E2F family(E2Fs)in head and neck squamous cell carcinoma(HNSCC)by bioinformatics methods,and investigate the role of E2Fs in HNSCC.Methods The public databases of TCGA,GEPIA2,and UALCAN were used to analyze the mRNA expression of E2Fs in HNSCC and the relationship with overall survival(OS)of HNSCC′s patients,while cBioPortal database was used to screen co-expression genes of E2Fs to construct a co-expression network,and R software was used to deeply analyze the biological functions of E2Fs and their co-expression genes.Results Eight E2Fs were significantly overexpressed in HNSCC than those in adjacent tissues,with E2F4 the highest expression level,followed by E2F1,E2F6 and E2F7.Several significant positive correlations were found between E2Fs members with Spearman analysis.Gene Ontology analysis showed that E2Fs and their 93 co-expressed genes mainly participated in regulating several biological processes,such as DNA replication and chromosome separation,through DNA replication,cell cycle,Fanconi anemia and other signal pathways.Cox univariate and multivariate analysis showed that the high expression of E2F4(HR=1.502,95%CI:1.141-1.977)and E2F8(HR=0.698,95%CI:0.531-0.917)was associated with the OS of HNSCC;and the nomogram showed that the patients with high E2F4 expression had the lowest survival probability with one-year OS,followed by patients with low E2F8 expression.Conclusion E2F family were highly expressed in HNSCC,the high mRNA expression of E2F4 and E2F8 were related to the prognosis of HNSCC,and E2Fs and their targets were mainly involved in biological processes,such as cell chromosome separation and DNA replication,through DNA replication,cell cycle,Fanconi anemia and other signaling pathways.