慢性牙周炎与慢性阻塞性肺疾病的潜在共同分子机制及其转录因子初探

doi:10.7518/hxkq.2023.2022489

摘要/Abstract

摘要：

目的探讨慢性牙周炎（CP）和慢性阻塞性肺疾病（COPD）之间潜在的cross-talk基因、相关通路和转录因子。方法从GEO数据库下载CP（GSE10334和GSE16134）和COPD（GSE76925）的基因表达谱，进行差异表达分析、功能聚类分析、构建蛋白质相互作用（PPI）网络，通过4种拓扑分析算法和模块划分筛选出核心cross-talk基因，再进行功能聚类分析。结果 GSE10334共筛选出164个差异表达基因（DEG）（119个上调、45个下调）；GSE16134共筛选出208个DEG（154个上调、54个下调）；GSE76925共筛选出1 408个DEG（557个上调、851个下调）。PPI网络包括21个节点和20条边。最终筛选出7个核心基因CD79A、FCRLA、CD19、IRF4、CD27、SELL和CXCL13，相关通路为原发性免疫缺陷，B细胞受体信号通路和细胞因子-细胞因子受体相互作用。其得分最高的转录因子为IRF4。结论本研究探索了CP和COPD的潜在共同发病机制，其cross-talk基因、相关通路和转录因子可能为进一步的机制研究提供新思路。

关键词: 慢性牙周炎, 慢性阻塞性肺疾病, cross-talk基因, 转录因子

Abstract:

Objective To investigate possible cross-talk genes, associated pathways, and transcription factors between chronic periodontitis (CP) and chronic obstructive pulmonary disease (COPD). Methods The gene expression profiles of CP (GSE10334 and GSE16134) and COPD (GSE76925) were downloaded from the GEO database. Differential expression and functional clustering analyses were performed. The protein‑protein interaction (PPI) network was constructed. The core cross-talk genes were filtered using four topological analysis algorithms and modular segmentation. Then, functional clustering analysis was performed again. Results GSE10334 detected 164 differentially expressed genes (DEGs) (119 upregulated and 45 downregulated). GSE16134 identified 208 DEGs (154 upregulated and 54 downregulated). GSE76925 identified 1 408 DEGs (557 upregulated and 851 downregulated). The PPI network included 21 nodes and 20 edges. The final screening included seven cross-talk genes: CD79A, FCRLA, CD19, IRF4, CD27, SELL, and CXCL13. Relevant pathways included primary immunodeficiency, the B-cell receptor signaling pathway, and cytokine-cytokine receptor interaction. Conclusion This study indicates the probability of shared pathophysiology between CP and COPD, and their cross-talk genes, associated pathways, and transcription factors may offer novel concepts for future mechanistic investigations.

Key words: chronic periodontitis, chronic obstructive pulmonary disease, cross-talk gene, transcription factor

中图分类号:

R 781.4⁺2

张晨, 候珍珍, 宗颖睿. 慢性牙周炎与慢性阻塞性肺疾病的潜在共同分子机制及其转录因子初探[J]. 华西口腔医学杂志, 2023, 41(5): 533-540.

Zhang Chen, Hou Zhenzhen, Zong Yingrui.. Exploratory research on the probable shared molecular mechanism and transcription factors between chronic periodontitis and chronic obstructive pulmonary disease[J]. West China Journal of Stomatology, 2023, 41(5): 533-540.

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疾病	数据集	芯片平台	病例样本数/ 个	对照样本数/ 个	总样本数/ 个	上调DEG数/ 个	下调DEG数/ 个	总DEG数/ 个	\|log₂FC\|	P值
CP	GSE10334	GPL570	183	64	247	119	45	164	>1	<0.05
	GSE16134	GPL570	241	69	310	154	54	208	>1	<0.05
COPD	GSE76925	GPL10558	111	40	151	557	851	1408	>0.5	<0.05

基因名	全称	MCC	MNC	Degree	EPC
CD19	白细胞分化抗原	116	10	10	6.243
IRF4	干扰素调节因子4	96	7	7	5.739
CD79A	细胞抗原受体复合体相关蛋白a链	90	8	8	5.839
CD27	TNF受体超家族7	78	7	7	5.628
TNFRSF17	肿瘤坏死因子受体超家族成员17	54	6	6	5.335
SELL	选择素L	54	6	6	5.460
POU2AF1	B细胞特异性转录因子	36	6	6	5.227
CXCL13	CXC基序趋化因子配体13	30	5	5	4.915
FCRLA	Fc受体样A	12	4	4	4.630
CXCL12	CXC基序趋化因子配体12	8	4	4	4.412

类别	条目	功能	P值	校正P值	基因名	数目
生物学过程	GO：0030098	淋巴细胞分化	4.20×10^-6	7.381×10^-4	CD19/CD27/CD79A/IRF4	4
	GO：0002460	基于免疫受体体细胞重组的适应性免疫应答	4.60×10^-6	7.381×10^-4	CD19/CD27/IRF4/CXCL13	4
	GO：0030183	B细胞分化	1.16×10^-5	1×10^-3	CD19/CD27/CD79A	3
细胞定位	GO：0009897	细胞外围	2.59×10^-4	4×10^-3	CD19/CD27/CD79A	3
	GO：0045121	脂筏	5×10^-3	1.9×10^-3	CD19/CD79A	2
	GO：0098857	膜微区	5×10^-3	1.9×10^-3	CD19/CD79A	2
分子功能	GO：0008201	肝素结合	1×10^-3	2.5×10^-3	SELL/CXCL13	2
	GO：0005539	糖胺聚糖结合	2×10^-3	2.5×10^-3	SELL/CXCL13	2
	GO：1901681	硫化合物结合	3×10^-3	2.5×10^-3	SELL/CXCL13	2
KEGG	hsa05340	原发性免疫缺陷	3.20×10^-4	3×10^-3	CD19/CD79A	2
	hsa04662	B细胞受体信号通路	1×10^-3	7×10^-3	CD19/CD79A	2
	hsa04060	细胞因子-细胞因子受体相互作用	1.8×10^-3	6×10^-2	CD27/CXCL13	2

转录因子	NES	目标基因数目	目标基因
IRF4	9.880	4	FCRLA/IRF4/CXCL13/CD19
ELF1	8.966	4	FCRLA/CD79A/IRF4/CD19
GSC	8.780	5	CXCL13/CD27/CD19/FCRLA/IRF4
GATA1	8.416	2	CXCL13/IRF4
PAX3	7.979	4	IRF4/CD19/CD27/SELL
SRF	7.785	2	CD19/IRF4
PAX8	7.599	4	IRF4/SELL/CXCL13/CD27

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