|本期目录/Table of Contents|

[1]陈铮,郜洪宇,朱东望,等.生物信息学联合实验验证鉴定牙周炎牙周膜关键标志物[J].天津医科大学学报,2026,32(01):61-68.[doi:10.20135/j.issn.1006-8147.2026.01.0061]
　CHEN Zheng,GAO Hongyu,ZHU Dongwang,et al.Identification of key biomarkers of periodontal membrane in periodontitis using integrated bioinformatics and experimental validation[J].Journal of Tianjin Medical University,2026,32(01):61-68.[doi:10.20135/j.issn.1006-8147.2026.01.0061]
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生物信息学联合实验验证鉴定牙周炎牙周膜关键标志物(PDF)

《天津医科大学学报》[ISSN:1006-8147/CN:12-1259/R]

卷:
32卷
期数:
2026年01期
页码:
61-68
栏目:
基础医学
出版日期:
2026-01-20

文章信息/Info

Title:
Identification of key biomarkers of periodontal membrane in periodontitis using integrated bioinformatics and experimental validation
文章编号:
1006-8147(2026)01-0061-08
作者:
陈铮; 郜洪宇; 朱东望; 成功
（天津医科大学口腔医学院，口腔医院牙周科；天津市口腔软硬组织修复再生重点实验室；天津医科大学口腔研究所，天津300070）
Author(s):
CHEN Zheng;  GAO Hongyu;  ZHU Dongwang;  CHENG Gong
（Department of Periodontics， Tianjin Medical University School and Hospital of Stomatology； Tianjin Key Laboratory of Oral Soft and Hard Tissues Restoration and Regeneration； Tianjin Medical University Institute of Stomatology，Tianjin 300070， China）
关键词:
牙周炎; 牙周膜; 生物信息学; 细胞黏附; PI3K-Akt信号通路
Keywords:
Key words periodontitis; periodontal membrane; bioinformatics; cell adhesion; PI3K-Akt signaling pathway
分类号:
R781.4
DOI:
10.20135/j.issn.1006-8147.2026.01.0061
文献标志码:
A
摘要:
目的：利用生物信息学联合临床样本，分析牙周膜关键标志物在牙周炎中的变化与机制。方法：从GEO数据库下载GSE27993、GSE75695两个数据集，统计分析均在 R 4.3.3（R Core Team， 2024）中完成，使用“limma”程序包筛选差异基因并进行GO功能富集与KEGG通路富集分析。利用STRING和Cytoscape构建蛋白-蛋白相互作用（PPI）网络来获取Hub基因，利用EPIC算法分析比较正常组与炎症组患者牙周膜组织的免疫细胞浸润类型及水平。临床中纳入牙周正常者6名，Ⅲ或Ⅳ期C级牙周炎患者6例，分为正常组和炎症组。收集牙周膜组织，放入RNAwait中保存备用。使用TRIzol法提取牙周膜组织mRNA，qPCR法检测正常组和炎症组Hub基因的表达水平。结果：通过生物信息学分析，共筛选出202个差异表达基因，构建PPI网络后获取了9个Hub基因，分别是CD34、KDR、VWF、CD36、TEK、SELE、HGF、FLT1、KIT，炎症组的9个Hub基因的表达水平显著高于对照组。通过GO功能富集与KEGG通路富集分析，9个Hub基因显著富集于信号转导受体活性和分子转导活性、蛋白酪氨酸激酶活性等多种分子功能以及磷脂酰肌醇3激酶（PI3K）-蛋白激酶B（Akt）、Rap1、Ras、丝裂原活化蛋白激酶（MAPK）等信号通路。通过EPIC算法发现，与正常组相比，炎症组患者的牙周膜组织中B细胞、CD8＋T细胞比例显著升高（t=2.594、2.118，均P＜0.05），而血管内皮细胞的比例显著降低（t=2.763，P＜0.05）。通过临床样本检测进一步验证Hub基因，与正常组相比，炎症组牙周膜的9个Hub基因表达水平显著升高（t=4.47、2.72、2.48、3.45、3.88、4.09、2.61、2.66、3.17，均P＜0.05），与生物信息学分析结果一致。结论：CD34、KDR、VWF、CD36、TEK、SELE、HGF、FLT1、KIT是牙周炎患者牙周膜中的关键生物标志分子。
Abstract:
Objective： To identify the changes and mechanisms of key biomarkers in the periodontal membrane of periodontitis by integrating bioinformatics with clinical samples. Methods： Two datasets GSE27993 and GSE75695 were downloaded from GEO. All statistical analyses were performed in R 4.3.3 （R Core Team， 2024）. The "limma" package was used to screen differentially expressed genes （DEGs）， followed by GO functional and KEGG pathway enrichment. Protein-protein interaction （PPI） networks were constructed using STRING and Cytoscape to obtain hub genes. The EPIC algorithm was employed to analyze and compare immune-cell infiltration patterns and levels in periodontal membrane tissues from healthy individuals and periodontitis patients. Clinically， six healthy subjects and six stage Ⅲ/Ⅳ grade C periodontitis patients were enrolled and allocated to healthy and inflamed groups. Periodontal membrane fragments were collected and preserved in RNAwait. Total mRNA was extracted with TRIzol， and qPCR was applied to quantify hub-gene expression in healthy and inflamed groups. Results： Bioinformatics identified 202 DEGs. Nine hub genes were extracted from the PPI network： CD34， KDR， VWF， CD36， TEK， SELE， HGF， FLT1 and KIT.The expression levels of the 9 Hub genes were significantly up-regulated in the inflamed group compared to the healthy group. GO functional enrichment and KEGG pathway enrichment analysis showed 9 hub genes were significantly involved in various molecular functions such as receptor signaling activity， molecular transducer activity， protein-tyrosine-kinase activity， as well as pathways such as phosphatidylinositol 3-kinase （PI3K）-protein kinase B （Akt）， Rap1， Ras， mitogen activated protein kinase （MAPK） and other signaling pathways. EPIC algorithm revealed proportions of B cells and CD8+ T cells was significantly increased （t=2.594， 2.118， both P<0.05） and endothelial cells was significantly decreased （t=2.763， P<0.05） in the periodontal membrane tissue of periodontitis patients compared to the healthy group. Further validation of Hub genes was conducted through clinical sample testing. Compared with the normal group， the expression of all nine hub genes in the periodontal membrane of the inflamed group were significantly elevated （t=4.47， 2.72， 2.48， 3.45， 3.88， 4.09， 2.61， 2.66， 3.17， all P<0.05）， consistent with the bioinformatic findings. Conclusion： CD34， KDR， VWF， CD36， TEK， SELE， HGF， FLT1 and KIT serve as key biomarkers in the periodontal membrane of periodontitis patients.

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备注/Memo

备注/Memo:
基金项目:国家自然科学基金青年项目（82101030）
作者简介:陈铮（1999-），男，硕士在读，研究方向：牙周病学；
通信作者:郜洪宇，E-mail：gaohongyu_frank@163.com。
更新日期/Last Update: 2026-01-15