转录因子CREB3L1在甲状腺癌组织中的表达及生物学意义

Expression and biological significance of transcription factor CREB3L1 in thyroid carcinoma

目的探讨转录因子环腺苷酸响应元件结合蛋白3-样1(CREB3L1)在甲状腺癌(THCA)组织中的表达及其临床意义。方法从GEO、ArrayExpress、SRA、TCGA等数据库检索下载CREB3L1 mRNA在THCA组织中的表达谱,应用Wilcoxon非参数检验检测CREB3L1 mRNA在THCA组织和正常甲状腺组织中表达水平的差异;计算CREB3L1表达值的标准化均数差(SMD)及汇总受试者工作特征(SROC)曲线下面积等指标,综合评估CREB3L1 mRNA在THCA组织中的表达水平及其对THCA的区分能力。用上述数据集批量获取CREB3L1在THCA组织中的相关过表达基因,应用CistromeDB预测CREB3L1转录靶基因,用clusterProfiler对CREB3L1在THCA组织中的相关过表达基因、CREB3L1转录靶标交集基因进行基因本体和京都基因与基因组百科全书功能注释。在THPA数据库中查看CREB3L1蛋白在THCA组织中的表达水平。结果与正常甲状腺组织比较,THCA组织中CREB3L1蛋白表达水平呈上调趋势。基于基因芯片、高通量测序数据集共纳入1175例THCA组织和791例正常甲状腺组织样本。CREB3L1 mRNA在THCA组织中呈高表达[SMD=0.11,95%可信区间(95%CI):0.01~0.20],集成SROC曲线下面积为0.62(95%CI:0.57~0.66)。CREB3L1蛋白在THCA组织中高表达患者5年生存率比低表达者低。交叉基因主要富集在细胞周期信号通路上,主要生物学功能为细胞器裂解。细胞分裂周期6蛋白(CDC6)与CREB3L1呈正相关。结论CREB3L1在THCA组织中高表达不利于患者的预后,有可能通过靶向基因CDC6参与了THCA的发生、发展。

Objective To investigate the expression of transcription factor cyclic adenosine monophosphate responsive element binding protein 3-like 1(CREB3L1)in thyroid carcinoma(THCA)tissues and its clinical significance.Methods The CREB3L1 mRNA expression profiles in THCA tissues were retrieved and downloaded from GEO,ArrayExpress,SRA and TCGA databases.The difference of CREB3L1 mRNA expression between THCA and normal thyroid tissues was detected by Wilcoxon nonparametric test.The standardized mean difference(SMD)of CREB3L1 expression values and the area under the curce(AUC)of summary receiver operating characteristic(SROC)curve were calculated to comprehensively assess the expression level of CREB3L1 mRNA in THCA tissues and its ability to discriminate between THCA.The above dataset was used to obtain the relevant overexpressed genes of CREB3L1 in THCA tissues in bulk.CistromeDB was used to predict CREB3L1 transcription target genes.The gene ontology and Kyoto Encyclopedia of Genes and Genomes were annotated by clusterProfiler for CREB3L1 related overexpressed genes and CREB3L1 transcriptional target intersection genes in THCA tissues.The expression level of CREB3L1 protein in THCA tissues was examined in the THPA database.Results Compared with normal thyroid tissues,the expression level of CREB3L1 protein in THCA tissues was up-regulated.A total of 1175 THCA and 791 normal thyroid tissue samples were included based on gene chip and high-throughput sequencing data sets.It was confirmed that CREB3L1 mRNA was highly expressed in THCA tissues(SMD=0.11,95%CI:0.01-0.20),SROC AUC=0.62(95%CI:0.57-0.66).The five-year survival rate of patients with high expression of CREB3L1 protein in THCA tissues was lower than that of patients with low expression.Cross genes were mainly concentrated in cell cycle pathway and their main biological function was organelle lysis.Cell division cycle 6 protein(CDC6)was positively correlated with CREB3L1.Conclusion The high expression of CREB3L1 in THCA tissues is not conducive to the prognosis of patients,and it is possible that the targeted gene CDC6 is involved in the occurrence and development of THCA.