ORIGINAL RESEARCH article
Front. Med.
Sec. Rheumatology
Volume 12 - 2025 | doi: 10.3389/fmed.2025.1578016
Overlapping Genes Connect Rheumatoid Arthritis and Head and Neck Cancer: Coincidence or Shared Immune Pathophysiology?
Provisionally accepted
- 1Minzu University of China, Beijing, China
- 2Beijing Tongren Hospital, Capital Medical University, Beijing, Beijing Municipality, China
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Despite advances in understanding the pathophysiology of rheumatoid arthritis (RA) and head and neck cancer (HNC) individually, their shared genetic and molecular mechanisms remain poorly defined. This study aimed to explore gene-level connections between RA and HNC. A comprehensive literature mining approach identified gene-disease associations from PubMed and bioinformatics databases, covering 19,924 genes. An AI-driven computational pipeline applied the Adjusted Binomial Method Algorithm (ABMA) to assess association reliability. Overlapping genes were analyzed through protein-protein interaction (PPI) networks, functional annotation, and literature-based pathway analyses to elucidate common and distinct mechanisms. The analysis identified 3,697 RA-related and 6,249 HNC-related genes, supported by 13,555 and 16,096 references, respectively, with a significant overlap of 2,549 genes (OR = 7.52; p < 1×10⁻¹⁶). Statistical refinement yielded 224 significant RA genes and 421 significant HNC genes, including 35 overlapping genes (OR = 9.27; p = 1.63×10⁻²⁰), which formed a dense PPI network (206 edges; density = 0.17; clustering coefficient = 0.67). Seven key hub genes-TLR2, RAC1, RELA, CTSK, CDC42, CXCL11, and CYP2C19-emerged as central nodes in immune and inflammatory regulation. Functional enrichment analysis identified nine significantly enriched pathways or categories, including inflammatory response, chemotaxis, and the chemokine signaling pathway. Pathway analysis further revealed a bidirectional regulatory loop linking RA and HNC via five of these hub genes (RELA, CDC42, CTSK, CXCL11, and CYP2C19), which mediate feedback mechanisms in immune-inflammatory signaling. These findings highlight robust immuno-inflammatory mechanisms that may serve as shared therapeutic targets for both conditions.
Keywords: Rheumatoid arthritis, head and neck cancer, AI-driven computational process, protein-protein interaction, pathways, Genetic mechanisms
Received: 01 Mar 2025; Accepted: 03 Jun 2025.
Copyright: © 2025 Wang, Li, Yang and Lian. 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: Meng Lian, Beijing Tongren Hospital, Capital Medical University, Beijing, 100730, Beijing Municipality, China
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