基因富集及Meta分析对影响肝癌发生发展关键基因的筛选

目的:筛选影响肝癌发生发展的关键基因.方法:运用跨种属肿瘤基因筛选策略比较不同种属的肝癌基因表达谱间的相似改变,选择5套不同种属的肝癌基因表达芯片分别通过基因组富集(gene set enrichment analysis,GSEA)以及对单套数据集单个基因元分析(meta-analysis,Meta)的分析方法,筛选出在转录水平上影响肝癌的基因.结果:用GSEA方法分析,5组数据中所得通路对比,上调中皆有的通路为氨基糖核苷酸糖代谢、细胞周期、甲状腺癌;下调中皆有的通路为亚油酸代谢、花生四烯酸代谢.对单套数据集单个基因进行Meta分析,共筛出P<0.05的基因1708个.用DAVID和KEGG网站的分析工具发现这1708个差异基因中有720个基因能够在KEGG库中筛出,主要分布在细胞周期、卵母细胞减数分裂、DNA复制等通路.这两种分析方法得出的通路中,重叠性较高的主要为细胞周期通路.在细胞周期通路中差异性有统计学意义(P<0.05)的基因25个,文献报道其中5个基因与肝癌有密切联系.结论:可能影响肝癌发生发展的信号传导通路是细胞周期通路,后续我们将对细胞周期通路里的显著性基因进行验证.

Applying gene set enrichment analysis and meta-analysis to screen key genes controlling the development and progression of hepatic carcinoma

AIM:To analyze vast amounts of hepatic carcinoma-related microarray data and identify crucial genes that control the development and progression of hepatocellular carcinoma(HCC).METHODS:Cross-species comparison could be used to explore the similarities between HCCrelated gene expression prof iles of human beings and other species.In order to screen genes that are involved in hepatocarcinogenesis,gene set enrichment analysis(GSEA) and meta-analysis were performed to study f ive gene expression data sets of independent species.RESULTS:Among the five gene expression data sets,three up-regulated and two downregulated pathways were found to be consistent by gene set enrichment analysis.The upregulated pathways are amino sugar and nucleotide sugar metabolism,cell cycle,and thyroid cancer,while the down-regulated pathways are linoleic acid metabolism and arachidonic acid metabolism.A total of 1 708 genes with a P < 0.05 were found in meta-analysis for five datasets,of which 720 could be assigned to functional pathways by DAVID and KEGG.These pathways include cell cycle,oocyte meiosis,and DNA replication.Cell cycle is the overlapping significant pathway between the two methods.Twenty-five genes with a P < 0.05 were identified in meta-analysis of cell cycle pathway.Five significant genes may be involved in the occurrence and progression of HCC.CONCLUSION:Cell cycle may be the crucial pathway to affect signal transduction in hepatocarcinogenesis.