大肠癌转移过程中所涉及的细胞信号调控网络非常复杂,寻找调控网络中的关键调控点对阐明大肠癌转移机制以及寻找药物治疗靶点均具有重要意义。研究表明,CREB5(cAMP responsive element binding protein 5)可能为大肠癌转移相关信号调控网络中的关键基因。文章基于大肠癌表达谱数据,根据CREB5基因表达值的大小对大肠癌的相关分子事件进行了富集分析,发现这些分子事件与肿瘤转移密切相关。根据CREB5能够和c-Jun结合成为异二聚体的特点,联合分析转录因子AP-1结合位点的富集情况,筛选出在CREB5基因高表达组中表达上调、具有AP-1结合位点、且属于癌症通路的基因16个,这些基因所构成的分子网络与细胞迁移功能类相关度最高。细胞迁移功能类主要由5个基因——CSF1R、MMP9、PDGFRB、FIGF和IL6所构成,因此CREB5可能是通过调控这5个关键基因进而促进大肠癌的转移。
The purpose of this study was to screen key survival-related genes from patients with colorectal cancer and explore signal transduction network of the involved genes.In a previous study,survival-related genes of patients with colorectal cancer were selected by colorectal cancer-related expression data GSE17538 using the Significance Analysis of Microarrays(SAM3.01)software,and 235 genes related to the survival of patients with colorectal cancer were obtained.Therefore,the following screening and analysis were conducted on these 235 genes in this study.First,the enrichment analysis of transcription factor binding sites was conducted on the 235 genes.Genes with more than seven transcription factor binding sites were screened.Then,these genes and upregulated genes in colorectal cancer were intersected.Finally,survival analysis and regulatory network analysis were conducted on the screened genes.This allowed clarification of the relationship between these genes and the survival of patients with colorectal cancer and the signaling network involving these genes in the cell signal transduction network of colorectal cancer.Through the above analysis,six upregulated genes in colorectal cancer related to the survival of colorectal cancer patients and highly regulated by transcription factors were selected,namely STX2,PODXL,KLK6,GRB10,EHBP1 and CREB5.These genes are involved in signal regulatory networks related to colorectal cancer metastasis-related signaling pathways.Therefore,the survival of patients with colorectal cancer is closely correlated with colorectal cancer metastasis.The six survival-related genes affect the survival of patients by regulating colorectal cancer metastasis-associated signaling pathways.
