Overlapping genes connect rheumatoid arthritis and head and neck cancer: coincidence or shared immune pathophysiology?
IntroductionDespite 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.MethodsThis study aimed to explore gene-level connections between RA and HNC. A comprehensiv...
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Frontiers Media S.A.
2025-06-01
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmed.2025.1578016/full |
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| author | Ran Wang Haiyang Li Haiyang Li Yifan Yang Yifan Yang Meng Lian Meng Lian |
| author_facet | Ran Wang Haiyang Li Haiyang Li Yifan Yang Yifan Yang Meng Lian Meng Lian |
| author_sort | Ran Wang |
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| description | IntroductionDespite 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.MethodsThis 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.ResultsThe 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.ConclusionThese findings highlight robust immuno-inflammatory mechanisms that may serve as shared therapeutic targets for both conditions. |
| format | Article |
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| language | English |
| publishDate | 2025-06-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Medicine |
| spelling | doaj-art-56e6e42b80b14ded90cf334c3dcd50de2025-08-20T02:35:50ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2025-06-011210.3389/fmed.2025.15780161578016Overlapping genes connect rheumatoid arthritis and head and neck cancer: coincidence or shared immune pathophysiology?Ran Wang0Haiyang Li1Haiyang Li2Yifan Yang3Yifan Yang4Meng Lian5Meng Lian6School of Pharmacy, Key Laboratory of Ethnomedicine of Ministry of Education, Minzu University of China, Beijing, ChinaDepartment of Otorhinolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, ChinaKey Laboratory of Otorhinolaryngology Head and Neck Surgery (Capital Medical University), Ministry of Education, Beijing, ChinaDepartment of Otorhinolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, ChinaKey Laboratory of Otorhinolaryngology Head and Neck Surgery (Capital Medical University), Ministry of Education, Beijing, ChinaDepartment of Otorhinolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, ChinaKey Laboratory of Otorhinolaryngology Head and Neck Surgery (Capital Medical University), Ministry of Education, Beijing, ChinaIntroductionDespite 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.MethodsThis 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.ResultsThe 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.ConclusionThese findings highlight robust immuno-inflammatory mechanisms that may serve as shared therapeutic targets for both conditions.https://www.frontiersin.org/articles/10.3389/fmed.2025.1578016/fullrheumatoid arthritishead and neck cancerAI-driven computational processprotein–protein interactionpathwaysgenetic mechanisms |
| spellingShingle | Ran Wang Haiyang Li Haiyang Li Yifan Yang Yifan Yang Meng Lian Meng Lian Overlapping genes connect rheumatoid arthritis and head and neck cancer: coincidence or shared immune pathophysiology? Frontiers in Medicine rheumatoid arthritis head and neck cancer AI-driven computational process protein–protein interaction pathways genetic mechanisms |
| title | Overlapping genes connect rheumatoid arthritis and head and neck cancer: coincidence or shared immune pathophysiology? |
| title_full | Overlapping genes connect rheumatoid arthritis and head and neck cancer: coincidence or shared immune pathophysiology? |
| title_fullStr | Overlapping genes connect rheumatoid arthritis and head and neck cancer: coincidence or shared immune pathophysiology? |
| title_full_unstemmed | Overlapping genes connect rheumatoid arthritis and head and neck cancer: coincidence or shared immune pathophysiology? |
| title_short | Overlapping genes connect rheumatoid arthritis and head and neck cancer: coincidence or shared immune pathophysiology? |
| title_sort | overlapping genes connect rheumatoid arthritis and head and neck cancer coincidence or shared immune pathophysiology |
| topic | rheumatoid arthritis head and neck cancer AI-driven computational process protein–protein interaction pathways genetic mechanisms |
| url | https://www.frontiersin.org/articles/10.3389/fmed.2025.1578016/full |
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