原发性抗磷脂综合征患者中性粒细胞关键基因的生物信息学分析

doi:10.3969/j.issn.1674-490X.2022.01.002

医学研究与教育 ›› 2022, Vol. 39 ›› Issue (1): 8-14.DOI: 10.3969/j.issn.1674-490X.2022.01.002

原发性抗磷脂综合征患者中性粒细胞关键基因的生物信息学分析

林梅英,甘东辉,高颖,王正杰,陈志敏

莆田学院附属医院, 福建莆田 351100

收稿日期:2021-12-10 出版日期:2022-02-25 发布日期:2022-02-25
通讯作者: 陈志敏(1994—),男,福建莆田人,医师,在读博士,主要从事生物信息学与内科系统疾病研究。E-mail: chenzm0905@163.com
作者简介:林梅英(1986—),女,福建莆田人,主管护师,主要从事血液风湿内分泌系统疾病护理与基础研究。 E-mail: linmeiying999@163.com
基金资助:
莆田学院校内科研项目(2019040,2019044)

Identification and bioinformatics analysis of key neutrophil genes in patients with primary antiphospholipid syndrome

LIN Meiying, GAN Donghui, GAO Ying, WANG Zhengjie,CHEN Zhimin

Affiliated Hospital of Putian College, Putian 351100, China

Received:2021-12-10 Online:2022-02-25 Published:2022-02-25

摘要/Abstract

摘要： 目的通过生物信息学方法筛选原发性抗磷脂综合征(antiphospholipid syndrome, APS)患者中性粒细胞中的关键差异基因,并鉴定其参与的生物功能和信号通路。方法在GEO数据库中下载APS患者中性粒细胞的RNA测序数据,使用R语言中的limma包筛选差异表达基因,通过clusterProfiler包分别对上调和下调基因进行基因本体论(gene ontology, GO)和京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes, KEGG)富集分析。最后,通过STRING数据库构建蛋白-蛋白互作网络,使用Cytoscape软件计算网络中的核心基因。结果共筛选得到512个上调基因,473个下调基因,上调基因主要参与的功能和通路包括固有免疫反应调节、中性粒细胞激活、炎症复合体形成等,下调基因主要参与的功能和通路包括T细胞激活、淋巴细胞分化、淋巴细胞激活等。IFIT1、IFI35、IFI3、CCL2、TLR8、FCGR1A是核心的上调基因。MYC、CD8A、FYN、CD28、LCK、GNB2L1是核心的下调基因。结论通过生物信息学方法分析出的核心基因可能是APS患者中性粒细胞发挥免疫效应的关键靶点。

关键词: 抗磷脂综合征, 中性粒细胞, hub基因, 免疫效应

Abstract: Objective To screen key differential genes and identify the biological functions and signaling pathways involved in neutrophils from patients with primary antiphospholipid syndrome(APS)by bioinformatic methods. Methods RNA sequencing data of neutrophils from APS patients were downloaded from the GEO database, differentially expressed genes were screened by using the limma package in R language, and up- and down-regulated genes were subjected to gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis by clusterProfiler, respectively. Finally, protein-protein interaction network was constructed by STRING database and core genes in the network were calculated using cytoscape software. Results A total of 512 up-regulated genes and 473 down-regulated genes were obtained by limma package screening. Up-regulated genes were mainly involved in functions and pathways including regulation of innate immune response, neutrophil activation, inflammatory complex formation, etc. down-regulated genes were mainly involvedin functions and pathways including T cell activation, lymphocyte differentiation, lymphocyte activation, etc. IFIT1, IFI35, IFI3, CCL2, TLR8, FCGR1A were the core genes among the up-regulated genes. MYC, CD8A, FYN,CD28, LCK, GNB2L1 were the core genes among the down-regulated genes. Conclusion The core genes identified by bioinformatic methods may be the key targets for the immune effects of neutrophils in patients with primary antiphospholipid syndrome.

Key words: antiphospholipid syndrome, neutrophils, hub gene, immune effect

中图分类号:

R446

林梅英,甘东辉,高颖,王正杰,陈志敏. 原发性抗磷脂综合征患者中性粒细胞关键基因的生物信息学分析[J]. 医学研究与教育, 2022, 39(1): 8-14.

LIN Meiying, GAN Donghui, GAO Ying, WANG Zhengjie,CHEN Zhimin. Identification and bioinformatics analysis of key neutrophil genes in patients with primary antiphospholipid syndrome[J]. Journal of Hebei Medical College for Continuing Education, 2022, 39(1): 8-14.

参考文献

[1] GARCIA D, ERKAN D. Diagnosis and management of the antiphospholipid syndrome[J]. N Engl J Med, 2018, 378(21): 2010-2021. DOI: 10.1056/NEJMra1705454.
[2] SCHREIBER K, SCIASCIA S, DE GROOT P G, et al. Antiphospholipid syndrome[J]. Nat Rev Dis Primers, 2018, 4: 17103. DOI: 10.1038/nrdp.2017.103.
[3] LU Y, DONG Y, ZHANG Y, et al. Antiphospholipid antibody-activated NETs exacerbate trophoblast and endothelial cell injury in obstetric antiphospholipid syndrome[J]. J Cell Mol Med, 2020, 24(12): 6690-6703. DOI: 10.1111/jcmm.15321.
[4] WIRESTAM L, ARVE S, LINGE P, et al. Neutrophils-important communicators in systemic lupus erythematosus and antiphospholipid syndrome[J]. Front Immunol, 2019, 10: 2734. DOI: 10.3389/fimmu.2019.02734.
[5] LI K N, DU Y X, LI L, et al. Bioinformatics approaches for anti-cancer drug discovery[J]. Curr Drug Targets, 2020, 21(1): 3-17. DOI: 10.2174/1389450120666190923162203.
[6] KNIGHT J S, MENG H, COIT P, et al. Activated signature of antiphospholipid syndrome neutrophils reveals potential therapeutic target[J]. JCI Insight, 2017, 2(18): e93897. DOI: 10.1172/jci.insight.93897.
[7] NEGRINI S, PAPPALARDO F, MURDACA G, et al. The antiphospholipid syndrome: from pathophysiology to treatment[J]. Clin Exp Med, 2017, 17(3): 257-267. DOI: 10.1007/s10238-016-0430-5.
[8] DOBROWOLSKI C, ERKAN D. Treatment of antiphospholipid syndrome beyond anticoagulation[J]. Clin Immunol, 2019, 206: 53-62. DOI: 10.1016/j.clim.2018.03.001.
[9] XOURGIA E, TEKTONIDOU M G. Type I interferon gene expression in antiphospholipid syndrome: pathogenetic, clinical and therapeutic implications[J]. J Autoimmun, 2019, 104: 102311. DOI: 10.1016/j.jaut.2019.102311.
[10] PALLI E, KRAVVARITI E, TEKTONIDOU M G. Type I interferon signature in primary antiphospholipid syndrome: clinical and laboratory associations[J]. Front Immunol, 2019, 10: 487. DOI: 10.3389/fimmu.2019.00487.
[11] KIM B, YEON J W, LEE J H, et al. CCL2 mitigates cyclic AMP-suppressed Th2 immune response in human dendritic cells[J]. Allergy, 2020, 75(8): 2108-2111. DOI: 10.1111/all.14284.
[12] HURST J, PRINZ N, LORENZ M, et al. TLR7 and TLR8 ligands and antiphospholipid antibodies show synergistic effects on the induction of IL-1beta and caspase-1 in monocytes and dendritic cells[J]. Immunobiology, 2009, 214(8): 683-691. DOI: 10.1016/j.imbio.2008.12.003.
[13] SCHWARZER R, JIAO H P, WACHSMUTH L, et al. FADD and caspase-8 regulate gut homeostasis and inflammation by controlling MLKL-and GSDMD-mediated death of intestinal epithelial cells[J]. Immunity, 2020, 52(6): 978-993. DOI: 10.1016/j.immuni.2020.04.002.

原发性抗磷脂综合征患者中性粒细胞关键基因的生物信息学分析

Identification and bioinformatics analysis of key neutrophil genes in patients with primary antiphospholipid syndrome

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 1

编辑推荐

Metrics

本文评价