基于GEO结直肠癌芯片数据的生物信息学分析

Bioinformatics analysis of colorectal cancer genome microarray based on GEO database

目的利用生物信息学分析方法，挖掘结直肠癌（CRC）的关键基因并探索其发病机制。方法在公共基因芯片数据库（GEO）中下载结直肠癌表达谱芯片数据，在GCBI实验室中筛选出结直肠癌显著差异的基因，分别对显著差异基因作GO富集分析、KEGG通路分析、蛋白质相互作用（PPI）网络分析。进一步利用cytoscape将PPI结果建立互作模块。结果通过差异分析得出在正常结直肠组织、结直肠腺瘤、结直肠癌中表达量逐步明显下调的基因有492个，逐步明显上调的有248个，共有740个显著差异基因。GO富集分析主要体现在各种代谢过程、细胞增殖、信号调节、RNA聚合酶II转录因子活性等。KEGG信号通路主要富集在癌症转录失调、细胞周期及p53信号通路等。并利用互作模型筛选出CDK1、MCM2、CDC6、CCNA1、CCNB2、CDKN1B、ORC1、E2F1、CHEK1、PCNA等45个与结直肠癌发生发展关系密切的关键基因。关键基因主要富集在细胞周期、病毒致癌机理、癌症相关、p53及P13K—Akt等信号通路。结论通过生物信息学对基因芯片数据的分析，能获取结直肠癌的关键基因及其相关通路，为后续研究提供依据。

Objective To explore the key genes and pathogenesis of colorectal cancer （CRC） by bioinformatics analysis. Methods The microarray data of whole genome expression profiles containing normal colorectal tissue, colorectal adenoma, and colorectal cancer were downloaded from the GEO and identified differential expression genes （DEGs） of colorectal cancer by GCBI. The DEGs were analyzed by gene ontology （GO）, KEGG pathway, and protein-protein interaction （PPI） network. Then, the interaction model was established by cytoscape using PPI results. Results A total of 740 DEGs （248 upregulated and 492 downregulated） were obtained when gene expression gradually increased or gradually reduced in normal colorectal tissue, colorectal adenoma tissue, and colorectal cancer tissue. GO analysis results showed that DEGs were significantly enriched in metabolic processes, cell proliferation, regulation of signaling, and RNA polymerase II transcription factor activity. KEGG pathway analysis showed the DEGs were enriched in transcriptional misregulation in cancer, cell cycle and p53 signaling pathway and so on. The key genes related to colorectal cancer including CDK1, MCM2, CDC6, CCNA1, CCNB2, CDKN1B, ORC1, E2F1, CHEK1, PCNA were obtained from the interaction model. Then, KEGG pathway analysis showed the key genes were enriched in cell cycle, viral carcinogenesis, pathways in cancer, p53 signaling pathway, and PI3K-Akt signaling pathway. Conclusion The key genes and their related pathways in colorectal cancer were obtained from bioinformatics analysis of gene chip data and provided the basis for follow-up study.