基于生物信息学的慢性胰腺炎发病机制探讨研究

Research on the Pathogenesis of Chronic Pancreatitis Based on Bioinformatics

目的:通过生物信息学方法分析慢性胰腺炎转录组表达数据集,探讨其发病的可能机制。方法:利用差异基因分析,明确GSE65146中造模后14d与正常对照组差异基因表达的情况,并对差异基因进行GO及KEGG分析。利用差异基因建立蛋白相互作用网络后选取关键基因进行分析。并利用免疫浸润分析明确慢性胰腺炎模型的免疫浸润情况。结果:慢性胰腺炎模型与对照组共有426个差异基因,其中包括297个上调基因及129个下调基因。GO分析提示差异基因的主要生物学功能富集于趋化作用、伤口愈合、调节肽酶活性、白细胞迁移、蛋白质加工、细胞趋化等生物学过程。KEGG分析提示细胞因子—细胞因子受体相互作用通路可能参与慢性胰腺炎的发生及发展。建立PPI网络后共选取8个关键差异基因(Cd44、Fn1、Ccr2、Ccr5、Tlr4、Ccl3、Fcgr3、Itga2)。免疫浸润分析提示巨噬细胞浸润可能参与了慢性胰腺炎的发病过程。结论:Ccl3、Ccr2及Ccr5作为重要的趋化作用因子,可能通过细胞因子—细胞因子受体相互作用信号通路发挥募集巨噬细胞的作用,从而介导慢性胰腺炎的病理发生过程。

Objective:Analyze the transcriptome expression dataset of chronic pancreatitis by bioinformatics methods to explore the possible mechanisms of its pathogenesis.Methods:Differential gene analysis was utilized to clarify the expression of differential genes in GSE65146 at 14 days after modeling and normal controls,and GO and KEGG analyses were performed on the differential genes.The key genes were selected for analysis after establishing protein interaction networks using differential genes.And immune infiltration analysis was used to clarify the immune infiltration of chronic pancreatitis model.Results:There were 426 differential genes in the chronic pancreatitis model compared with the control group,including 297 up-regulated genes and 129 down-regulated genes,and GO analysis suggested that the main biological functions of differential genes were enriched in chemotaxis,wound healing,regulation of peptidase activity,migration of leukocytes,protein processing,and cellular chemotaxis,etc.KEGG analysis suggested that the cytokine-cytokine receptor interaction pathway might be involved in the occurrence and development of chronic pancreatitis.A total of 8 key differential genes(Cd44,Fn1,Ccr2,Ccr5,Tlr4,Ccl3,Fcgr3,Itga2)were selected after establishing the PPI network.Immune infiltration analysis suggested that macrophage infiltration might be involved in the pathogenesis of chronic pancreatitis.Conclusion:Ccl3,Ccr2 and Ccr5,as important chemotactic factors,may play a role in recruiting macrophages through the cytokine-cytokine receptor interaction signaling pathway,thus mediating the pathogenesis of chronic pancreatitis.