基于基因芯片整合分析筛选慢性牙周炎相关基因和转录因子

doi:10.7518/hxkq.2021.06.003

华西口腔医学杂志 ›› 2021, Vol. 39 ›› Issue (6): 633-641.doi: 10.7518/hxkq.2021.06.003

基于基因芯片整合分析筛选慢性牙周炎相关基因和转录因子

曾小丽¹(), 李生娇¹, 单铮男¹, 殷俊豪¹, 姜吉蕊¹, 郑章龙¹, 李家²()

^1.上海牙组织修复与再生工程技术研究中心，同济大学附属口腔医院·;同济大学口腔医学院口腔颌面外科，上海 200072
^2.上海牙组织修复与再生工程技术研究中心，同济大学附属口腔医院·;同济大学口腔医学院修复科，上海 200072

收稿日期:2020-09-21 修回日期:2021-07-09 出版日期:2021-12-01 发布日期:2021-12-03
通讯作者: 李家 E-mail:aqua1905@tongji.edu.cn;lj2014@tongji.edu.cn
作者简介:曾小丽，硕士，E-mail：aqua1905@tongji.edu.cn
基金资助:
上海市科学技术委员会项目(19140904800)

Identification of hub genes and transcription factors involved in periodontitis on the basis of multiple microarray analysis

Zeng Xiaoli¹(), Li Shengjiao¹, Shan Zhengnan¹, Yin Junhao¹, Jiang Jirui¹, Zheng Zhanglong¹, Li Jia²()

^1.Shanghai Engineering Research Center of Tooth Restoration and Regeneration; Dept. of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Tongji University, Shanghai 200072, China
^2.Shanghai Engineering Research Center of Tooth Restoration and Regeneration; Dept. of Prosthodontics, School and Hospital of Stomatology, Tongji University, Shanghai 200072, China

Received:2020-09-21 Revised:2021-07-09 Online:2021-12-01 Published:2021-12-03
Contact: Li Jia E-mail:aqua1905@tongji.edu.cn;lj2014@tongji.edu.cn
Supported by:
Science and Technology Commission Project of Shanghai(19140904800)

摘要/Abstract

摘要： 目的

利用生物信息学技术分析中重度牙周炎患者炎性病变牙龈组织与健康牙龈组织间基因表达的差异。

方法

使用基因表达数据分析工具GEO2R从牙周炎数据集GSE10334与GSE16134中筛选差异表达基因并取交集。应用g: Profiler功能富集分析工具，分别对上调及下调基因进行基因本体分析和通路分析。利用在线STRING检索工具构建蛋白相互作用（PPI）网络，并在Cytoscape软件中进行可视化及进一步分析，包括使用cytoHubba、MCODE和iRegulon等插件进行核心基因、关键模块鉴定和转录因子预测。

结果

共筛选出196个牙周炎差异基因，其中上调基因139个，下调基因57个；上调基因参与了免疫系统、病毒蛋白与细胞因子及细胞因子受体的相互作用、细胞因子-细胞因子受体相互作用、白细胞跨内膜迁移和趋化因子受体结合趋化因子等免疫反应相关途径，而下调基因则涉及了角质化包膜形成、角化等途径。PPI网络中处于核心位置的基因为CXC基序趋化因子配体（CXCL）8、CXCL1、CXC 基序趋化因子受体（CXCR）4、选择素（SEL）L、CD19和IKAROS家族锌指（IKZF）1。PPI网络关键模块分别参与趋化因子应答、B细胞受体信号通路和白细胞介素应答。iRegulon预测结果显示，转录因子干扰素调节因子（IRF）4可信度最高。

结论

牙周炎的发病机制与牙龈组织中CXCL8、CXCL1、CXCR4、SELL、CD19和IKZF1等基因的表达变化密切相关，转录因子IRF4可能是重要的上游调控因子。

关键词: 牙周炎, 基因表达综合数据库, 生物信息学分析, 差异表达基因

Abstract: Objective

To identify the differentially expressed genes (DEGs) during the pathogenesis of periodontitis by bioinformatics analysis.

Methods

GEO2R was used to screen DEGs in GSE10334 and GSE16134. Then, the overlapped DEGs were used for further analysis. g:Profiler was used to perform Gene Ontology analysis and pathway analysis for upregulated and downregulated DEGs. The STRING database was used to construct the protein-protein interaction (PPI) network, which was further visua-lized and analyzed by Cytoscape software. Hub genes and key modules were identified by cytoHubba and MCODE plug-ins, respectively. Finally, transcription factors were predicted via iRegulon plug-in.

Results

A total of 196 DEGs were identified, including 139 upregulated and 57 downregulated DEGs. Functional enrichment analysis showed that the upregulated DEGs were mainly enriched in immune-related pathways including immune system, viral protein interaction with cytokine and cytokine receptor, cytokine-cytokine receptor interaction, leukocyte transendothelial migration, and chemokine receptors bind chemokines. On the contrary, the downregulated DEGs were mainly related to the formation of the cornified envelope and keratinization. The identified hub genes in the PPI network were CXCL8, CXCL1, CXCR4, SEL, CD19, and IKZF1. The top three modules were involved in chemokine response, B cell receptor signaling pathway, and interleukin response, respectively. iRegulon analysis revealed that IRF4 scored the highest.

Conclusion

The pathogenesis of periodontitis was closely associated with the expression levels of the identified hub genes including CXCL8, CXCL1, CXCR4, SELL, CD19, and IKZF1. IRF4, the predicted transcription factor, might serve as a dominant upstream regulator.

Key words: periodontitis, gene expression omnibus database, bioinformatics analysis, differentially expressed genes

中图分类号:

R 781.4

曾小丽, 李生娇, 单铮男, 殷俊豪, 姜吉蕊, 郑章龙, 李家. 基于基因芯片整合分析筛选慢性牙周炎相关基因和转录因子[J]. 华西口腔医学杂志, 2021, 39(6): 633-641.

Zeng Xiaoli, Li Shengjiao, Shan Zhengnan, Yin Junhao, Jiang Jirui, Zheng Zhanglong, Li Jia. Identification of hub genes and transcription factors involved in periodontitis on the basis of multiple microarray analysis[J]. West China Journal of Stomatology, 2021, 39(6): 633-641.

图/表 5

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参考文献 18

1	Souto GR, Queiroz CM Jr, Costa FO, et al. Relationship between chemokines and dendritic cells in human chronic periodontitis[J]. J Periodontol, 2014, 85(10): 1416-1423.
2	Figueredo CM, Lira-Junior R, Love RM. T and B cells in periodontal disease: new functions in a complex scenario[J]. Int J Mol Sci, 2019, 20(16): E3949.
3	Slots J. Periodontitis: facts, fallacies and the future[J]. Periodontol 2000, 2017, 75(1): 7-23.
4	Papapanou PN, Behle JH, Kebschull M, et al. Subgingival bacterial colonization profiles correlate with gingival tissue gene expression[J]. BMC Microbiol, 2009, 9: 221.
5	Demmer RT, Behle JH, Wolf DL, et al. Transcriptomes in healthy and diseased gingival tissues[J]. J Periodontol, 2008, 79(11): 2112-2124.
6	Tsuchida S. Proteome analysis of molecular events in oral pathogenesis and virus: a review with a particular focus on periodontitis[J]. Int J Mol Sci, 2020, 21(15): E5184.
7	Davanian H, Stranneheim H, Båge T, et al. Gene expression profiles in paired gingival biopsies from periodontitis-affected and healthy tissues revealed by massively pa-rallel sequencing[J]. PLoS One, 2012, 7(9): e46440.
8	Finoti LS, Nepomuceno R, Pigossi SC, et al. Association between interleukin-8 levels and chronic periodontal disease: a PRISMA-compliant systematic review and meta-analysis[J]. Medicine (Baltimore), 2017, 96(22): e6932.
9	Rath-Deschner B, Memmert S, Damanaki A, et al. CXCL1, CCL2, and CCL5 modulation by microbial and biomechanical signals in periodontal cells and tissues—in vitro and in vivo studies[J]. Clin Oral Investig, 2020, 24(10): 3661-3670.
10	Hajishengallis G, Wang M, Liang S, et al. Pathogen induction of CXCR4/TLR2 cross-talk impairs host defense function[J]. Proc Natl Acad Sci U S A, 2008, 105(36): 13532-13537.
11	McIntosh ML, Hajishengallis G. Inhibition of Porphyromonasgingivalis-induced periodontal bone loss by CXCR4 antagonist treatment[J]. Mol Oral Microbiol, 2012, 27(6): 449-457.
12	Hajishengallis G. New developments in neutrophil biology and periodontitis[J]. Periodontol 2000, 2020, 82(1): 78-92.
13	Jego G, Bataille R, Pellat-Deceunynck C. Interleukin-6 is a growth factor for nonmalignant human plasmablasts[J]. Blood, 2001, 97(6): 1817-1822.
14	Carter RH, Fearon DT. CD19: lowering the threshold for antigen receptor stimulation of B lymphocytes[J]. Scien-ce, 1992, 256(5053): 105-107.
15	Kawai T, Matsuyama T, Hosokawa Y, et al. B and T lymphocytes are the primary sources of RANKL in the bone resorptive lesion of periodontal disease[J]. Am J Pathol, 2006, 169(3): 987-998.
16	Georgopoulos K. The making of a lymphocyte: the choi-ce among disparate cell fates and the IKAROS enigma[J]. Genes Dev, 2017, 31(5): 439-450.
17	Rodríguez-Carrio J, López P, Alperi-López M, et al. IR-F4 and IRGs delineate clinically relevant gene expression signatures in systemic lupus erythematosus and rhe-umatoid arthritis[J]. Front Immunol, 2018, 9: 3085.
18	Hajishengallis G. Periodontitis: from microbial immune subversion to systemic inflammation[J]. Nat Rev Immunol, 2015, 15(1): 30-44.

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基于基因芯片整合分析筛选慢性牙周炎相关基因和转录因子

Identification of hub genes and transcription factors involved in periodontitis on the basis of multiple microarray analysis

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