[1]于 帆,楼 爽,黄婷婷,等.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[J].现代检验医学杂志,2023,38(02):13-17,31.[doi:10.3969/j.issn.1671-7414.2023.02.003 ]
　YU Fan,LOU Shuang,HUANG Ting-ting,et al.Exploring Gastrointestinal Acute Graft-Versus-Host Disease-Related Genes and Their Pathogenic Mechanisms Based on GEO Database[J].Journal of Modern Laboratory Medicine,2023,38(02):13-17,31.[doi:10.3969/j.issn.1671-7414.2023.02.003 ]
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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()

《现代检验医学杂志》[ISSN:/CN:]

卷:
第38卷
期数:
2023年02期
页码:
13-17,31
栏目:
论著
出版日期:
2023-03-15

文章信息/Info

Title:
Exploring Gastrointestinal Acute Graft-Versus-Host Disease-Related Genes and Their Pathogenic Mechanisms Based on GEO Database
文章编号:
1671-7414（2023）02-013-06
作者:
于 帆，楼 爽，黄婷婷，何海洪，周义文
（南方医科大学深圳医院临床检验医学中心，广东深圳 518000）
Author(s):
YU Fan，LOU Shuang，HUANG Ting-ting，HE Hai-hong，ZHOU Yi-wen
（Clinical Laboratory Medical Center, Shenzhen Hospital of Southern Medical University, Guangdong Shenzhen 518000, China）
关键词:
移植物抗宿主病; 异基因造血干细胞移植; 细胞因子风暴; 生物信息学
分类号:
R457.7；R446
DOI:
10.3969/j.issn.1671-7414.2023.02.003
文献标志码:
A
摘要:
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及细胞因子风暴相关通路； IfiTM3，Ifi6和 Ifi44等干扰素诱导蛋白编码基因主要通过干扰素 -MAPK通路参与机体免疫反应； STAT1同时参与了上述两类基因涉及的生物学功能过程。结论 CXCL9，CXCL10和 CXCL11等趋化因子配体编码基因， IfiTM3，Ifi6和 Ifi44等干扰素诱导蛋白编码基因及 STAT1基因与胃肠道急性移植物抗宿主病炎症发展进程及细胞因子风暴高度相关，具有成为相关诊疗靶点的潜力。
Abstract:
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.

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备注/Memo

备注/Memo:
收稿日期：2022-12-14修回日期：2023-01-10
基金项目：国家自然科学基金青年科学基金项目（82002974）；吴阶平医学基金会 -临床科研专项资助基金（320.6750.2021-06-30）；南方医科大学深圳医院重点学科建设基金（ZDXKKYTS006）；南方医科大学深圳医院“后三甲”科研基金（22H3AZF05）。
作者简介：于帆（1996-），男，硕士研究生，主管技师，主要从事临床检验诊断学及生物信息学。 E-mail: ninja_yu@outlook.com。
通讯作者：周义文（1965-），男，博士研究生，主任技师，主要从事临床检验诊断学及分子生物学。 E-mail: yiwenzhou21@aliyun.com。

更新日期/Last Update: 2023-03-15