Proliferative verrucous and homogeneous Leukoplakias exhibit differential methylation patterns
[EN] Objective: Proliferative verrucous leukoplakia (PVL) is considered a clinically distinct entity from other forms of oral leukoplakia (OL) due to its unique presentation and progressive nature. However, the molecular differences between PVL and other OL subtypes remain unclear. This study aimed...
| Autores: | , , , , |
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| Tipo de recurso: | artículo |
| Fecha de publicación: | 2025 |
| País: | España |
| Institución: | Universitat Politècnica de València (UPV) |
| Repositorio: | RiuNet. Repositorio Institucional de la Universitat Politécnica de Valéncia |
| Idioma: | inglés |
| OAI Identifier: | oai:riunet.upv.es:10251/224445 |
| Acceso en línea: | https://riunet.upv.es/handle/10251/224445 |
| Access Level: | acceso abierto |
| Palabra clave: | Differential methylation Homogeneous leukoplakia Oral leukoplakia Oral squamous cell carcinoma Proliferative verrucous leukoplakia |
| Sumario: | [EN] Objective: Proliferative verrucous leukoplakia (PVL) is considered a clinically distinct entity from other forms of oral leukoplakia (OL) due to its unique presentation and progressive nature. However, the molecular differences between PVL and other OL subtypes remain unclear. This study aimed to investigate whether DNA methylation differences exist between PVL and homogeneous leukoplakia (HL). Materials and Methods: Oral biopsy samples were collected from 12 patients with PVL, 8 with HL, and 10 healthy individuals. A genome-wide DNA methylation analysis was performed using the Infinium EPIC platform. Results: A total of 1,815 differentially methylated CpG sites were identified between PVL and HL, with HL showing a prominent state of hypermethylation. These CpGs spanned 813 genes involved in key biological processes such as cell adhesion, extracellular matrix organization, and cellular/synaptic signaling. Notably, 43% of these genes have previously been associated with cancer and prognosis. A multinomial logistic regression model was developed to distinguish between HL, PVL, and healthy controls. The model, which achieved a cross-validated accuracy of 73%, incorporated differentially methylated, cancer-related genes including ADNP, BRCA2, CDK13, GNB1, NIN, NUMB, PIK3C2B, PTK2, SHISA4, THSD7B, WWP1, and ZNF292. Genes specifically altered in HL (MEN1, TNRC6B) and PVL (ACOXL, ADH1B, CAMTA1, CBFA2T3, CPXM2, LRFN2, SORCS2, and SPN) were also included. Conclusions: PVL and HL exhibit distinct methylation signatures that may underlie their differing clinical behaviors. These findings highlight the potential of DNA methylation markers as diagnostic tools and point to novel biomarkers for early detection and classification of oral leukoplakia subtypes. |
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