基于GEO数据库筛选胃肠道急性移植物抗宿主病相关基因及其致病机制分析

目的 筛选胃肠道急性移植物抗宿主病发生发展过程中的关键基因，探索其潜在致病及调控机制并初步评估其临床应用价值。方法 基于基因表达综合（gene expression omnibus,GEO）数据库下载异基因造血干细胞移植后患者直肠乙状结肠黏膜组织RNA-Seq数据集GSE168116，通过R软件limma包筛选胃肠道急性移植物抗宿主病患者黏膜组织表达水平上调基因；利用clusterProfiler包进行功能富集分析；基于String数据库和Cytoscape软件进行蛋白质互作网络构建及其关键子网络定位挖掘关键基因；通过Wikipathway插件进行代谢通路分析以探索其生物学功能。结果 在胃肠道急性移植物抗宿主病患者黏膜组织筛选表达水平上调基因132个；上述基因主要富集于机体防御反应、机体免疫系统相关进程以及细胞因子、干扰素及趋化因子相关免疫信号通路；在蛋白质互作网络中定位以STAT1,CXCL10,IFIT3,CXCL8,ISG15,OAS2,OASL,MX2,IFI44L及IFI6为核心基因的关键子网络；CXCL9,CXCL10和CXCL11等趋化因子配体编码基因广泛参与炎症发展进程...

Exploring Gastrointestinal Acute Graft-Versus-Host Disease-Related Genes and Their Pathogenic Mechanisms Based on GEO Database

Objective To screen the key genes in the occurrence and development of gastrointestinal acute graft-versus-host disease, to explore the potential pathogenic and regulatory mechanisms, and evaluate the application value for clinical diagnosis and treatment. Methods Based on the RNA-Seq data set (GSE168116) of rectosigmoid mucosa tissue of patients after allogeneic hematopoietic stem cell transplantation downloaded from gene expression omnibus（GEO）database, differential expression analysis was performed via limma to screen the up-regulated genes in mucosal tissue of patients with gastrointestinal acute graft-versus-host disease. Functional enrichment analysis was performed via clusterProfiler. Based on the construction of the protein interaction network and the positioning of the key sub-networks based on String and Cytoscape, the protein-coding genes with key roles were further mined, and their biological functions were explored through metabolic pathway analysis via Wikipathway. Results A total of 132 significantly up-regulated genes were screened in mucosal tissue of patients with gastrointestinal acute graft-versus-host disease. The above-mentioned genes were mainly enriched in defense response, immune system-related processes and a series of immune signaling pathways that are highly related to cytokines, interferons and chemokines. The protein interaction network was constructed and the key sub-networks involving STAT1, CXCL10, IfiT3, CXCL8, ISG15, OAS2, OASL, MX2, Ifi44L and Ifi6 were located. CXCL9, CXCL10, CXCL11 and other chemokine ligand-encoding genes were widely involved in the development of inflammation and cytokine storm-related pathways. Interferon-inducible protein-coding genes such as IfiTM3, Ifi6 and Ifi44 were mainly involved in immune response through the interferon-MAPK pathway. STAT1 was involved in the biological function process of both the above two types of genes. Conclusion CXCL9,CXCL10, CXCL11 and other chemokine ligand-encoding genes, IfiTM3, Ifi6, Ifi44 and other interferon-inducible protein-encoding genes and STAT1 gene were related to the inflammation development process and cytokine storms of gastrointestinal acute graft-versus-host disease, which indicates the potential to become the relevant diagnosis and treatment target for the disease.