溃疡性结肠炎与克罗恩病基因谱表达的差异

Differential gene expression profiles between ulcerative colitis and Crohn's disease

目的:探究溃疡性结肠炎(ulcerative colitis,UC)与克罗恩病(Crohn's disease,CD)两种肠道炎症疾病的发病机制,为临床治疗时的给药选择提供参考.方法:收集UC肠上皮细胞,CD肠上皮细胞,正常人肠上皮细胞,将他们进行基因芯片分析,从而拿到各自的基因表达谱.通过线形回归模型软件包limma对不同组的芯片进行差异比较,从而得到不同处理间的差异表达基因.利用数据库Gene Otology对基因功能定位的分类,通过cluster Profiler包进行GO聚类富集,将这些差异表达的基因从细胞内组成、分子功能和生物进程三方面上进行聚类,从而得到这些差异表达的基因对细胞的影响.利用DAVID网站对差异表达的基因进行KEGG PATHWAY的聚类分析,从而得到前UC与CD细胞发生改变的信号通路的异同之处.结果:通过差异分析,得到了UC、CD和正常细胞差异表达基因比较.GO结果显示UC和CD两种疾病确实存在着显著的差异,KEGG通路分析UC与CD细胞通路的一个重要区别在于信号传导方面,包括Cell adhesion molecules(CAMs)、ECM-receptor interaction、B cell receptor signaling pathway和Cytokine-cytokine receptor interaction.结论:两种疾病存在着上千个差异表达基因.其次,这两种疾病的细胞表现存在明显差异.最后,细胞内通路也存在差异,尤其是代谢上存在差异,因而可以通过代谢产物对这两种疾病以示区分.UC和CD这些分子水平上的差异,为临床上对这两种疾病的确诊提供了很好的思路.

AIM： To compare the difference in gene expression profiles between ulcerative colitis and Crohn’s disease to provide a theoretical basis for further understanding of their pathogenesis and clinical treatment of choice. METHODS： Intestinal epithelial cells from patients with Crohn’s disease, those with ulcerative colitis and healthy volunteers were subjected to microarray analysis to obtain their gene expression profiles. Linear regression model was built using the Limma package to compare differences in gene expression between different groups. Gene Ontology（GO） analysis was performed to predict gene function, and cluster Profiler was used to conduct enrichment analysis of gene clusters. KEGG pathway analysis was performed to obtain the similarities and differences in pathways between Crohn’s disease and ulcerative colitis. RESULTS： Differential gene expression profiles were obtained between ulcerative colitis, Crohn’s disease and normal controls by microarray analysis. GO analysis showed that ulcerative colitis and Crohn’s disease had significant differences in gene expression. KEGG pathway analysis indicated that ulcerative colitis and Crohn’s disease had significant differences in cell adhesion molecules（CAMs）, ECM-receptor interaction, B cell receptor signaling pathway, and cytokine-cytokine receptor interaction. CONCLUSION： There are thousands of differentially expressed genes between ulcerative colitis and Crohn’s disease. The two diseases have significant differences in intracellular pathways, particularly metabolism, and differential metabolites may be used to distinguish the two diseases.