乳腺导管原位癌浸润性进展相关基因的生物信息学研究

Bioinformatics Analysis of invasive progression-related genes in breast ductal carcinoma in situ

目的筛选介导乳腺导管原位癌(DCIS)浸润性进展的相关基因。方法从美国国立生物技术信息中心(NCBI)公共基因芯片(GEO)数据库下载含正常乳腺(NC)、DCIS和微小浸润乳腺癌(IBC)这3种类型样本的基因芯片;使用R软件包limma分析IBC与DCIS、DCIS与NC之间的差异表达基因;使用STEM软件对上述两组差异表达基因进行趋势分析,筛选出随着NC-DCISIBC的趋势表达水平逐渐变化的基因;对筛选出的差异表达的基因进行KEGG信号通路富集分析。结果通过对差异基因的趋势分析,筛选出12个随着NC-DCIS-IBC的趋势表达显著下调的基因,以及10个显著上调的基因,其中运动神经元和胰腺同源盒1(MNX1)、基质金属蛋白酶1(MMP-1)可能为介导DCIS浸润性进展的相关基因。信号通路富集分析结果显示,磷脂酰肌醇3-激酶/蛋白激酶B(PI3K/AKT)、黏附和细胞外基质/受体相互作用3个信号通路分子异常在DCIS发生及浸润性进展中均存在显著异常调控。结论MNX1、MMP-1可能为介导DCIS浸润性进展的相关基因,PI3K/AKT信号通路可能参与介导MNX1/MMP-1促进DCIS浸润性进展。

Objective To identify the key genes involved in the invasive progression of breast ductal carcinoma in situ(DCIS)by bioinformatics analysis.Methods Gene chips containing samples from normal mammary gland,breast DCIS and small invasive breast cancer(IBC)were downloaded from GEO database.The differentially expressed genes in DCIS compared to normal tissue samples,and in IBC compared to DCIS were analyzed by R language.Trend analysis of differentially expressed genes in the two groups was carried out by Short Time-series Expression Miner(STEM)software.The differentially expressed genes gradually changed with the trend of DCIS progression were screened out.Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis was performed on those differentially expressed genes.Results Through screening of differentially expressed genes,12 down-regulated genes and 10 up-regulated genes were screened with the invasive progression of DCIS,including MNX1 and MMP-1.Those differentially expressed genes in the KEGG pathway were significantly enriched in the PI3 K/AKT,cytokine-cytokine receptor interaction pathway and cell adhesion molecules.Conclusion MNX1 and MMP-1 might mediate invasive progression of breast DCIS,and PI3 K/AKT signaling may be involved in MNX1/MMP-1 regulation.