The association between diabetes and head and neck squamous cell carcinoma: evidence from clinical cohort and bioinformatics analyses

IntroductionDiabetes mellitus (DM) is a known risk factor for various cancers, but its relationship with head and neck squamous cell carcinoma (HNSCC) remains unclear. This study explores clinical and molecular links between DM and HNSCC through integrative analyses of patient data and bioinformatic...

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Main Authors: Yurong He, Jiaming Chen, Boxuan Han, Yanming Zhao, Lizhen Hou, Jugao Fang, Meng Lian
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-08-01
Series:Frontiers in Genetics
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Online Access:https://www.frontiersin.org/articles/10.3389/fgene.2025.1660012/full
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author Yurong He
Yurong He
Jiaming Chen
Boxuan Han
Boxuan Han
Yanming Zhao
Yanming Zhao
Lizhen Hou
Lizhen Hou
Jugao Fang
Jugao Fang
Meng Lian
Meng Lian
author_facet Yurong He
Yurong He
Jiaming Chen
Boxuan Han
Boxuan Han
Yanming Zhao
Yanming Zhao
Lizhen Hou
Lizhen Hou
Jugao Fang
Jugao Fang
Meng Lian
Meng Lian
author_sort Yurong He
collection DOAJ
description IntroductionDiabetes mellitus (DM) is a known risk factor for various cancers, but its relationship with head and neck squamous cell carcinoma (HNSCC) remains unclear. This study explores clinical and molecular links between DM and HNSCC through integrative analyses of patient data and bioinformatics.MethodsA 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. Literature-based data mining was used to extract gene–disease associations for DM and HNSCC, followed by functional enrichment, pathway and network analyses of overlapping genes.ResultsThe 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.ConclusionThese 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.
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spelling doaj-art-3fbc5c7b533a436cb7a979db5c90843f2025-08-20T03:36:53ZengFrontiers Media S.A.Frontiers in Genetics1664-80212025-08-011610.3389/fgene.2025.16600121660012The association between diabetes and head and neck squamous cell carcinoma: evidence from clinical cohort and bioinformatics analysesYurong He0Yurong He1Jiaming Chen2Boxuan Han3Boxuan Han4Yanming Zhao5Yanming Zhao6Lizhen Hou7Lizhen Hou8Jugao Fang9Jugao Fang10Meng Lian11Meng Lian12Department 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, ChinaThe 2nd Department of Head and Neck Surgery, Department of Oncoplastic Surgery, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 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, 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, ChinaIntroductionDiabetes mellitus (DM) is a known risk factor for various cancers, but its relationship with head and neck squamous cell carcinoma (HNSCC) remains unclear. This study explores clinical and molecular links between DM and HNSCC through integrative analyses of patient data and bioinformatics.MethodsA 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. Literature-based data mining was used to extract gene–disease associations for DM and HNSCC, followed by functional enrichment, pathway and network analyses of overlapping genes.ResultsThe 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.ConclusionThese 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.https://www.frontiersin.org/articles/10.3389/fgene.2025.1660012/fulldiabetes mellitushead and neck squamous cell carcinomacomorbiditygene overlapbioinformaticsco-occurrence modeling
spellingShingle Yurong He
Yurong He
Jiaming Chen
Boxuan Han
Boxuan Han
Yanming Zhao
Yanming Zhao
Lizhen Hou
Lizhen Hou
Jugao Fang
Jugao Fang
Meng Lian
Meng Lian
The association between diabetes and head and neck squamous cell carcinoma: evidence from clinical cohort and bioinformatics analyses
Frontiers in Genetics
diabetes mellitus
head and neck squamous cell carcinoma
comorbidity
gene overlap
bioinformatics
co-occurrence modeling
title The association between diabetes and head and neck squamous cell carcinoma: evidence from clinical cohort and bioinformatics analyses
title_full The association between diabetes and head and neck squamous cell carcinoma: evidence from clinical cohort and bioinformatics analyses
title_fullStr The association between diabetes and head and neck squamous cell carcinoma: evidence from clinical cohort and bioinformatics analyses
title_full_unstemmed The association between diabetes and head and neck squamous cell carcinoma: evidence from clinical cohort and bioinformatics analyses
title_short The association between diabetes and head and neck squamous cell carcinoma: evidence from clinical cohort and bioinformatics analyses
title_sort association between diabetes and head and neck squamous cell carcinoma evidence from clinical cohort and bioinformatics analyses
topic diabetes mellitus
head and neck squamous cell carcinoma
comorbidity
gene overlap
bioinformatics
co-occurrence modeling
url https://www.frontiersin.org/articles/10.3389/fgene.2025.1660012/full
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