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结直肠癌肝转移相关基因的生物信息学分析
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Abstract:
目的：通过对美国国家生物技术信息中心(NCBI)的GEO数据库现有的基因表达数据以及相关临床数据进行数据挖掘分析，以期寻找结直肠癌(Colorectal Cancer, CRC)肝转移发生的关键基因及治疗靶点。方法：对GEO数据库进行数据检索，筛选出包含正常结直肠组织、CRC组织以及CRC肝转移组织的基因芯片。采用GEO2R工具筛选CRC和正常结直肠组织的差异表达基因以及CRC与CRC肝转移之间的差异表达基因，进一步筛选出两基因集的共有差异表达基因。使用注释、注释可视化和集成发现数据库(DAVID)进行基因本体论(GO)分析和京都基因与基因组百科全书(KEGG)途径分析。利用STRING数据库和Cytoscape软件进行蛋白–蛋白互作(PPI)网络的构建和Hub基因的筛选。使用R语言分析Hub基因在正常结直肠、CRC以及CRC肝转移组织中的表达情况，使用基因表达谱交互分析(GEPIA)数据库分析Hub基因与CRC预后的相关性。结果：检索得到基因芯片GSE49355，CRC和正常结直肠组织的基因集中存在1394个差异表达基因，CRC与CRC肝转移的基因集中存在125个差异表达基因，两个基因集共有的差异表达基因有29个。GO分析显示，它们的生物学过程可能主要富集在补体激活、正向调节多肽酶活性、替代途径等；细胞学组分主要定位于血液微粒以及细胞外周；分子功能富集于补体和凝血级联、IL-17信号通路、肿瘤坏死因子信号通路等。KEGG信号通路的富集分析显示，差异基因主要富集于补体和凝血级联、IL-17信号通路、TNF信号通路等。对蛋白质相互作用分析中有关联的基因进行排序，前5个Hub基因为SPP1、MMP1、MMP3、CXCL1、CXCL5，它们在CRC中的表达均高于正常结直肠组织，SPP1的表达量在正常结直肠、CRC以及CRC肝转移组织逐渐增高，并且SPP1的高表达与CRC患者较差的生存显著相关。结论：SPP1、MMP1、MMP3、CXCL1、CXCL5与CRC肝转移具有相关性，或可为进一步研究CRC肝转移发生发展的分子机制提供一定基础。
Purpose: To find the key genes and therapeutic targets of liver metastasis of colorectal cancer (CRC) by mining and analyzing the existing gene expression data and related clinical data in the GEO database of the National Biotechnology Information Center (NCBI). Methods: The GEO database was searched, and the gene chips containing normal colorectal, CRC and liver metastatic tissues of CRC were screened. GEO2R tool was used to screen the differentially expressed genes (DEGs) between CRC and normal colorectal tissues and between CRC and liver metastasis of CRC, and the common DEGs of the two gene sets were further screened. Annotation, Visualization and Integrated Discovery Database (DAVID) was used for Gene Ontology (GO) analysis and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway analysis. STRING database and Cytoscape software were used to construct Protein-Protein Interaction (PPI) network and screen Hub genes. The expression of Hub genes in normal colorectal, CRC and liver metastatic tissues of CRC was analyzed by R language, and the correlation between Hub genes and the prognosis of CRC was analyzed by Gene Expression Profile Interactive Analysis (GEPIA) database. Results: The gene chip GSE49355 showed that there were 1394 genes in CRC and normal colorectal tissues, 125 genes in CRC and liver metastasis of CRC, and 29 DEGs in the two gene sets. GO analysis showed that their biological processes may be mainly concentrated in complement activation, positive regulation of polypeptidase activity, alternative pathway. Cellular components were mainly located in blood particles and peripheral cells. Molecular functions were enriched in peptidase activator activity, CXCR chemokine
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