子宫腺肌病在位内膜差异基因表达及信号转导网络构建

The expression and construction of signal net of differentially expressed genes in the eutopic endometria of adenomayosis

目的:探讨信使RNA(mRNA)在子宫腺肌病在位内膜组织中的差异表达情况,并构建差异基因间的信号转导网络。方法:收集4例子宫腺肌病患者的在位内膜组织及4例正常内膜组织。采用基因芯片检测mRNA表达,对差异表达的mRNA进行信号通路分析,得到差异基因参与的具有显著性、低误判率、靶向性的信号通路。基于KEGG数据库构建基因间的信号转导网络并得到网络中的关键基因。结果:子宫腺肌病在位内膜与对照内膜相比,有612个差异表达的mRNA,其中下调的有414个,上调的有198个。上调差异基因参与的显著性信号转导通路共40项,包括MAPK信号通路、局部黏附、黏附连接、PI3K-Akt信号通路等;下调差异基因参与的显著性信号转导通路共39项,包括DNA复制、细胞周期、细胞因子、细胞因子受体相互作用等。成功构建信号转导网络,得到网络中关键基因包括HDAC2和ACTN4等。结论:与正常内膜相比,子宫腺肌病在位内膜的mRNA存在明显的差异表达,可能与子宫腺肌病的发生发展密切相关。

Objective： To analyze the mRNAs expression diffrences in the eutopic endometria of women with adenomyosis and construct signal net of differentially expressed genes.Method： Eutopic endometria（ n = 4） were collected from patients with adenomyosis,and control endometria（ n = 4） were obtained from women without adenomyosis. The expression of mRNAs in both groups were detected by human gene microarray.Pathways analysis were applied to determine the significant,low false positive rate and targeted pathway that the differentially expressed genes involved.Based on the KEGG database,we constructed signal net of genes and got key genes in the net. Result： In total,612 mRNAs were identified with differential expression between endometria from patients with and without adenomyosis.Among these mRNAs,414 were significantly downregulated and 198 were significantly upregulated.Pathway analysis showed that40 pathways corresponded to up-regulated transcripts and that the enriched pathways included MAPK signaling pathway,focal adhesion,adherens junction,PI3K-Akt signaling pathway. With respect to down-regulated transcripts,there were 39 pathways corresponded and enriched pathways included DNA replication,cell cycle,cytokine-cytokine receptor interaction.We successfully constructed signal net and got key genes,included HDAC2,ACTN4 etc.Conclusion： The expression of mRNAs in the eutopic endometria were obviously different,which may have close relationship with the pathogenesis of adenomyosis.