Wang Ran, Li Haiyang, Yang Yifan, Lian Meng
School of Pharmacy, Key Laboratory of Ethnomedicine of Ministry of Education, Minzu University of China, Beijing, China.
Department of Otorhinolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, China.
Front Med (Lausanne). 2025 Jun 18;12:1578016. doi: 10.3389/fmed.2025.1578016. eCollection 2025.
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; < 1 × 10). Statistical refinement yielded 224 significant RA genes and 421 significant HNC genes, including 35 overlapping genes (OR = 9.27; = 1.63 × 10), 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.
尽管在分别理解类风湿性关节炎（RA）和头颈癌（HNC）的病理生理学方面取得了进展，但其共同的遗传和分子机制仍不清楚。
本研究旨在探索RA和HNC之间的基因水平联系。一种全面的文献挖掘方法从PubMed和生物信息学数据库中确定基因与疾病的关联，涵盖19,924个基因。一个由人工智能驱动的计算流程应用调整后的二项式方法算法（ABMA）来评估关联的可靠性。通过蛋白质-蛋白质相互作用（PPI）网络、功能注释和基于文献的通路分析对重叠基因进行分析，以阐明共同和不同的机制。
分析确定了3,697个与RA相关的基因和6,249个与HNC相关的基因，分别有13,555条和16,096条参考文献支持，其中有2,549个基因有显著重叠（OR = 7.52；<1×10）。统计精炼得出224个显著的RA基因和421个显著的HNC基因，包括35个重叠基因（OR = 9.27；=1.63×10），这些基因形成了一个密集的PPI网络（206条边；密度 = 0.17；聚类系数 = 0.67）。七个关键的枢纽基因——TLR2、RAC1、RELA、CTSK、CDC42、CXCL11和CYP2C19——成为免疫和炎症调节的中心节点。功能富集分析确定了九个显著富集的通路或类别，包括炎症反应、趋化作用和趋化因子信号通路。通路分析进一步揭示了一个双向调节环，通过这些枢纽基因中的五个（RELA、CDC42、CTSK、CXCL11和CYP2C19）将RA和HNC联系起来，它们在免疫炎症信号传导中介导反馈机制。
这些发现突出了强大的免疫炎症机制，这些机制可能是这两种疾病共同的治疗靶点。
