ORIGINAL RESEARCH article
Front. Genet.
Sec. Cancer Genetics and Oncogenomics
Volume 16 - 2025 | doi: 10.3389/fgene.2025.1660012
The Association between Diabetes and Head and Neck Squamous Cell Carcinoma: Evidence from Clinical Cohort and Bioinformatics Analyses
Provisionally accepted
- 1Department of Otorhinolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, 100730, Beijing, China
- 2Key Laboratory of Otorhinolaryngology Head and Neck Surgery (Capital Medical University), Ministry of Education, Beijing, China
- 3The 2nd Department of Head and Neck Surgery, Department of Oncoplastic Surgery, Hunan Cancer Hospital & the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, 410000, Changsha, China
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This study explores clinical and molecular connections between diabetes mellitus (DM) and head and neck squamous cell carcinoma (HNSCC) through an integrative analysis combining patient data and bioinformatics approaches. A retrospective cohort of 728 HNSCC patients was analyzed to assess sex-specific co-occurrence with DM. A simulation-based epidemiological model quantified associations based on observed clinical data and population incidence rates. Gene–disease associations for DM and HNSCC were identified through large-scale AI-assisted literature mining, followed by functional enrichment, pathway and network analyses of overlapping genes. The simulation revealed a significant association between DM and HNSCC, stronger in males (Odds Ratio [OR] = 3.03, p = 6.28 × 10⁻⁵⁰) than in females (OR = 2.18, p = 8.7 × 10⁻¹²). Data mining uncovered 3,489 overlapping genes (OR = 6.73, p < 4.95 × 10⁻³¹⁹), including nine key genes (GPX4, NLRP3, CASP3, HOTAIR, SRC, IGF2BP2, APP, CYP2C19, and PVT1) tightly interconnected and functionally enriched in inflammation, metabolism, and neurological signaling pathways. Four genes—CYP2C19, NLRP3, PVT1, and APP—appear central to DM's influence on HNSCC via the protein–protein interaction (PPI) network. These findings reveal a significant clinical and molecular connection between DM and HNSCC, especially in males, and highlight potential targets for future prevention and treatment strategies.
Keywords: Diabetes Mellitus, Head and neck squamous cell carcinoma, Comorbidity, Gene overlap, bioinformatics, Co-occurrence modeling, sex differences
Received: 05 Jul 2025; Accepted: 01 Aug 2025.
Copyright: © 2025 He, Chen, Han, Zhao, Hou, Fang 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, Department of Otorhinolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, 100730, Beijing, China
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