{"title":"HIF-1/2α: The Silent Architects of Adenoid Cystic Carcinoma-A Systematic Review and Meta-Analysis.","authors":"R Maheswari, Akhilesh Chandra, Rahul Agrawal","doi":"10.1111/odi.70048","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Adenoid cystic carcinoma (AdCC) is a rare, aggressive salivary gland malignancy with a poor prognosis due to metastasis and local recurrence. Although hypoxia-inducible factors-1/2α (HIF-1/2α) play crucial roles in AdCC, their pleiotropic effects remain poorly understood. This systematic review and meta-analysis evaluates the impact of HIF-1/2α in AdCC progression.</p><p><strong>Methods: </strong>A comprehensive literature search was conducted across PubMed, Scopus, EMBASE, and Web of Science to identify studies examining HIF-1/2α in AdCC. Study quality was assessed using the modified Newcastle-Ottawa scale, and meta-analyses were performed using IBM SPSS Statistics (Version 29).</p><p><strong>Results: </strong>Sixteen studies met inclusion criteria, with 10 studies encompassing 650 AdCC cases included in the meta-analysis. Positive HIF-1/2α expression was reported in 77.4% of AdCC cases (95% CI: 0.630-0.919, p < 0.001) and was significantly correlated with tumor size (OR: 0.38, 95% CI: 0.16-0.89, p = 0.03), advanced stage (OR: 2.86, 95% CI: 1.74-4.71, p < 0.001), and distant metastasis (OR: 1.82, 95% CI: 1.02-3.25, p = 0.04). Human studies demonstrated significantly increased HIF-1/2α protein and mRNA expression in AdCC cases compared to control groups. Solid-type AdCC exhibited predominantly higher nuclear HIF-1α expression than cribriform and tubular subtypes. Additionally, in cell culture models, the hypoxia-induced upregulation of these factors increased the expression of VEGF (20-fold), BNIP3 (6-fold), and NID1, promoting angiogenesis, epithelial-mesenchymal transition, autophagy, and invasiveness.</p><p><strong>Conclusion: </strong>HIF-1/2α emerge as a pivotal drivers of AdCC progression, serving dual roles as prognostic biomarker and therapeutic target, necessitating further clinical investigation through multicenter validation studies.</p>","PeriodicalId":19615,"journal":{"name":"Oral diseases","volume":" ","pages":""},"PeriodicalIF":2.9000,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Oral diseases","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1111/odi.70048","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"DENTISTRY, ORAL SURGERY & MEDICINE","Score":null,"Total":0}
引用次数: 0
Abstract
Background: Adenoid cystic carcinoma (AdCC) is a rare, aggressive salivary gland malignancy with a poor prognosis due to metastasis and local recurrence. Although hypoxia-inducible factors-1/2α (HIF-1/2α) play crucial roles in AdCC, their pleiotropic effects remain poorly understood. This systematic review and meta-analysis evaluates the impact of HIF-1/2α in AdCC progression.
Methods: A comprehensive literature search was conducted across PubMed, Scopus, EMBASE, and Web of Science to identify studies examining HIF-1/2α in AdCC. Study quality was assessed using the modified Newcastle-Ottawa scale, and meta-analyses were performed using IBM SPSS Statistics (Version 29).
Results: Sixteen studies met inclusion criteria, with 10 studies encompassing 650 AdCC cases included in the meta-analysis. Positive HIF-1/2α expression was reported in 77.4% of AdCC cases (95% CI: 0.630-0.919, p < 0.001) and was significantly correlated with tumor size (OR: 0.38, 95% CI: 0.16-0.89, p = 0.03), advanced stage (OR: 2.86, 95% CI: 1.74-4.71, p < 0.001), and distant metastasis (OR: 1.82, 95% CI: 1.02-3.25, p = 0.04). Human studies demonstrated significantly increased HIF-1/2α protein and mRNA expression in AdCC cases compared to control groups. Solid-type AdCC exhibited predominantly higher nuclear HIF-1α expression than cribriform and tubular subtypes. Additionally, in cell culture models, the hypoxia-induced upregulation of these factors increased the expression of VEGF (20-fold), BNIP3 (6-fold), and NID1, promoting angiogenesis, epithelial-mesenchymal transition, autophagy, and invasiveness.
Conclusion: HIF-1/2α emerge as a pivotal drivers of AdCC progression, serving dual roles as prognostic biomarker and therapeutic target, necessitating further clinical investigation through multicenter validation studies.
期刊介绍：
Oral Diseases is a multidisciplinary and international journal with a focus on head and neck disorders, edited by leaders in the field, Professor Giovanni Lodi (Editor-in-Chief, Milan, Italy), Professor Stefano Petti (Deputy Editor, Rome, Italy) and Associate Professor Gulshan Sunavala-Dossabhoy (Deputy Editor, Shreveport, LA, USA). The journal is pre-eminent in oral medicine. Oral Diseases specifically strives to link often-isolated areas of dentistry and medicine through broad-based scholarship that includes well-designed and controlled clinical research, analytical epidemiology, and the translation of basic science in pre-clinical studies. The journal typically publishes articles relevant to many related medical specialties including especially dermatology, gastroenterology, hematology, immunology, infectious diseases, neuropsychiatry, oncology and otolaryngology. The essential requirement is that all submitted research is hypothesis-driven, with significant positive and negative results both welcomed. Equal publication emphasis is placed on etiology, pathogenesis, diagnosis, prevention and treatment.
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