I González-Ruiz, P Ramos-García, H Boujemaoui-Boulaghmoudi, N Mjouel-Boutaleb, M A González-Moles
{"title":"Cancer Hallmarks Expression in Oral Leukoplakia: Systematic Review and Meta-Analysis.","authors":"I González-Ruiz, P Ramos-García, H Boujemaoui-Boulaghmoudi, N Mjouel-Boutaleb, M A González-Moles","doi":"10.1111/odi.70106","DOIUrl":null,"url":null,"abstract":"<p><strong>Objectives: </strong>To assess the available evidence on the expression of hallmarks of cancer and oral leukoplakia (OL) malignant transformation probability, with the goal of identifying the earliest oncogenic molecular events participating in oral cancer carcinogenesis.</p><p><strong>Methods: </strong>Embase, MEDLINE/PubMed, Scopus, and Web of Science were searched for primary-level studies published prior to Sept 24, strictly designed as longitudinal cohorts.</p><p><strong>Results: </strong>A total of 60 studies (9758 OLs) fulfilled the eligibility criteria, and the expression of 68 different biomarkers was evaluated using the immunohistochemical technique. Sustaining proliferation hallmark was frequently harbored by OLs (PP = 56.30%, 95% CI = 43.10-69.09), significantly associated with malignant transformation (RR = 1.92, 95% CI = 1.45-2.55, p < 0.001), and markedly more frequent than in normal oral mucosa (OR = 7.70, 95% CI = 2.22-26.65, p = 0.001). Also related, genome instability markers were considerably overexpressed and associated with oral cancer development (p < 0.05), although resulting from a smaller sample size. Another remarkable finding is related to the activation of proinvasive mechanisms in OLs, representing the epithelial-mesenchymal transition (EMT) phenomenon, which was frequent (PP = 37.30%, 95% CI = 28.21-46.86) and significantly associated with oral cancer (RR = 3.43, 95% CI = 2.67-4.40, p < 0.001). Finally, avoiding immune destruction markers were also overexpressed (PP = 35.77%, 95% CI = 24.66-47.69) and significantly higher in leukoplakias progressing to oral cancer (RR = 3.65, 95% CI = 1.87-7.13, p < 0.001).</p><p><strong>Conclusions: </strong>Malignant transformation of OL is significantly increased in hyperproliferative lesions, which develop the EMT phenomenon and avoid immune destruction through oncogenic mechanisms.</p>","PeriodicalId":19615,"journal":{"name":"Oral diseases","volume":" ","pages":""},"PeriodicalIF":2.9000,"publicationDate":"2025-09-30","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.70106","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
Objectives: To assess the available evidence on the expression of hallmarks of cancer and oral leukoplakia (OL) malignant transformation probability, with the goal of identifying the earliest oncogenic molecular events participating in oral cancer carcinogenesis.
Methods: Embase, MEDLINE/PubMed, Scopus, and Web of Science were searched for primary-level studies published prior to Sept 24, strictly designed as longitudinal cohorts.
Results: A total of 60 studies (9758 OLs) fulfilled the eligibility criteria, and the expression of 68 different biomarkers was evaluated using the immunohistochemical technique. Sustaining proliferation hallmark was frequently harbored by OLs (PP = 56.30%, 95% CI = 43.10-69.09), significantly associated with malignant transformation (RR = 1.92, 95% CI = 1.45-2.55, p < 0.001), and markedly more frequent than in normal oral mucosa (OR = 7.70, 95% CI = 2.22-26.65, p = 0.001). Also related, genome instability markers were considerably overexpressed and associated with oral cancer development (p < 0.05), although resulting from a smaller sample size. Another remarkable finding is related to the activation of proinvasive mechanisms in OLs, representing the epithelial-mesenchymal transition (EMT) phenomenon, which was frequent (PP = 37.30%, 95% CI = 28.21-46.86) and significantly associated with oral cancer (RR = 3.43, 95% CI = 2.67-4.40, p < 0.001). Finally, avoiding immune destruction markers were also overexpressed (PP = 35.77%, 95% CI = 24.66-47.69) and significantly higher in leukoplakias progressing to oral cancer (RR = 3.65, 95% CI = 1.87-7.13, p < 0.001).
Conclusions: Malignant transformation of OL is significantly increased in hyperproliferative lesions, which develop the EMT phenomenon and avoid immune destruction through oncogenic mechanisms.
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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