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目的探索结直肠癌(colorectal carcinoma,CRC)形成中的核心通路和关键基因。方法利用meta分析技术从以往5项CRC发生相关转录组学研究中筛选癌及癌旁差异表达基因。采用ComBat方法合并5项研究的癌组织基因表达谱数据,针对上述差异表达基因用PCIT软件进行共表达网络构建。利用CFinder软件揭示该共表达网络中存在的核心亚网络,并用Gather软件确定主要核心亚网络所富集的生物学功能。以重要核心亚网络(或通路)为重点,联合节点基因在CRC中的表达变化方向和相应染色体区域扩增或缺失的信息,发现亚网络功能形成中的候选驱动基因。结果 Meta分析转录组学研究共发现差异表达基因2 073个,其中在5项研究的癌组织中一致上调1 174个,一致下调899个,这些基因在CRC样本中形成的共表达网络包括798个基因节点和1 462条边,存在22个核心亚网络。最大的核心亚网络由77个基因和436条边组成,功能涉及细胞周期和增殖信号调控,UBE2C、MYBL2、FAM83 D、AURKA、TPX2等11个基因被预测为该信号功能的驱动基因。结论细胞周期和增殖信号通路是结直肠癌发生中的核心通路,UBE2C和AURKA等11个基因是该核心通路的驱动基因。
Objective To explore the core pathway and key genes in the formation of colorectal carcinoma (CRC). Methods Meta-analysis was used to screen differentially expressed genes between cancer and adjacent tissues from the previous five transcriptomics studies on CRC. ComBat method was used to combine the five studies of cancer gene expression profile data for the above-mentioned differentially expressed genes with PCIT software for co-expression network construction. CFinder software is used to reveal the core sub-networks existing in the co-expression network, and the Gather software is used to determine the biological functions enriched in the core sub-networks. With important core sub-networks (or pathways) as the focus, the joint node gene expression in CRC changes direction and the corresponding chromosomal region amplification or deletion of information, found in sub-network function of the candidate driver gene. Results A total of 2 073 differentially expressed genes were found in meta-analysis of transcriptomics, among which 1 174 were uniformly up-regulated in cancer tissues of the 5 studies and 899 were down-regulated. The co-expression networks of these genes in CRC samples included 798 Gene nodes and 1 462 sides, there are 22 core sub-networks. The largest core sub-network consists of 77 genes and 436 sides and functions are involved in the regulation of cell cycle and proliferation signaling. Eleven genes including UBE2C, MYBL2, FAM83D, AURKA and TPX2 are predicted to be driving genes for this signaling function. Conclusions Cell cycle and proliferation signaling pathways are the core pathways in the development of colorectal cancer. Eleven genes such as UBE2C and AURKA are the driving genes of this core pathway.