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ORIGINAL RESEARCH article

Front. Cell Dev. Biol.

Sec. Cellular Biochemistry

This article is part of the Research TopicBone Metabolism and Inflammatory ImmunityView all articles

Potential diagnostic markers and therapeutic targets for periodontitis with comorbid infective endocarditis based on bioinformatics and experimental analyses

Provisionally accepted
Feng  MeiFeng Mei1Wenjie  ZhangWenjie Zhang1Xinlin  WangXinlin Wang1Yutong  LiuYutong Liu1Xiangyu  ZhouXiangyu Zhou2Ting  ZhouTing Zhou3*Wei  ZhangWei Zhang4*
  • 1College & Hospital of Stomatology, Anhui Medical University, Heifei 230032, China
  • 2Hubei Minzu University‌, Enshi 445000, China
  • 3Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China
  • 4Department of Obstetrics and Gynaecology, The First Affiliated Hospital of Anhui Medical University, 218 Jixi Rd,, Hefei 230022, China

The final, formatted version of the article will be published soon.

Background: Periodontitis (PD) and infective endocarditis (IE) significantly impair quality of life and contribute to considerable socioeconomic burdens. Accumulating evidence supports a bidirectional interaction between these diseases that aggravates clinical outcomes. This study aims to identify diagnostic biomarkers and investigate therapeutic targets underlying PD-IE comorbidity. Methods: We analyzed disease-specific differentially expressed genes (DEGs) for PD and IE from datasets in the Gene Expression Omnibus (GEO). Functional enrichment analysis was then performed to investigate the biological roles of the DEGs in PD and IE datasets. Protein-protein interaction (PPI) networks were constructed using STRING database and hub genes were identified utilizing cytoHubba plugin in Cytoscape software. We selected diagnostic markers using a dual-algorithm approach that combined differential expression analysis and receiver operating characteristic (ROC) curve analysis, and subsequently evaluated their immune associations and therapeutic relevance. Our key findings were further validated using in vivo PD models. Results: A total of 22 DEGs were identified as common to both PD and IE. PPI analysis uncovered five hub genes. ROC curve analysis supported the diagnostic utility of these five markers. Following expression analysis, we identified 4 hub genes as potential diagnostic markers: ITGAM, FCGR3B, FCGR3A and ITGB2. Significant correlations were observed between the expression of these genes and immune cell infiltration in both diseases. In vivo experiments confirmed the upregulation of the potential diagnostic markers in PD tissues compared to normal controls. Conclusion: ITGAM, FCGR3B, FCGR3A, and ITGB2 can serve as mechanistically informative diagnostic biomarkers and promising therapeutic targets for PD-IE comorbidity. The shared pathophysiology of the two diseases involves immune response mechanisms. Our findings open up new avenues for the concurrent therapeutic targeting of both diseases.

Keywords: Infective endocarditis, Periodontitis, Hub gene, Bioinformatics analysis, immune cellsubtype relative proportion analysis

Received: 15 Oct 2025; Accepted: 06 Nov 2025.

Copyright: © 2025 Mei, Zhang, Wang, Liu, Zhou, Zhou and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Ting Zhou, zhoutingfy822@163.com
Wei Zhang, zhangwei@fy.ahmu.edu.cn

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