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RESEARCH PRODUCT

Differentially methylated genes in proliferative verrucous leukoplakia reveal potential malignant biomarkers for oral squamous cell carcinoma

Alejandro Herreros-pomaresJose V. BaganEloisa Jantus-lewintreAndrea MorenoSilvia Calabuig-fariñasLeticia BaganBeatriz SorianoCarlos Llorens

subject

Cancer ResearchMeDIP-seqBiology03 medical and health sciences0302 clinical medicinemedicineHumansMethylated DNA immunoprecipitationEpigeneticsDifferential methylation030223 otorhinolaryngologyBone morphogenesisSquamous Cell Carcinoma of Head and NeckOral cancerGATA3CancerBiomarkerDNA Methylationmedicine.diseaseRNAseqDifferentially methylated regionsOncologyOral squamous cell carcinomaCase-Control Studies030220 oncology & carcinogenesisDNA methylationCancer researchProliferative verrucous leukoplakiaMouth NeoplasmsEpigeneticsGene ontologyLeukoplakia OralOral SurgeryBiomarkersHOXD10

description

Objectives: To explore the pathophysiology of proliferative verrucous leucoplakia (PVL) through a methylated DNA immunoprecipitation and high-throughput sequencing (MeDIP-seq) case-control study. Materials and & nbsp; Methods: Oral biopsies from ten PVL patients and five healthy individuals were obtained and used to compare their epigenetic patterns. Network biology methods and integrative analyses of MeDIP-seq and RNAseq data were applied to investigate functional relations among differentially methylated genes (DMGs). The value of selected genes as malignant biomarkers was evaluated in a large cohort of oral squamous cell carcinoma (OSCC) patients from TCGA.& nbsp; Results: A total of 4647 differentially methylated regions were found, with a prominent state of hypermethylation in PVL patients. At the gene level, differentially methylated regions (DMRs) covered 826 genes with distinct roles, including transcription factors and binding proteins with functions in cell adhesion, migration, proliferation, regulation of transcription, bone morphogenesis, and cell signalling. Network analysis revealed three major hubs, two of them collecting proteins related to the response of the patients to PVL and treatment and one hub collecting proteins related to PVL and cancer. The integrative analysis revealed 8 genes (ARTN, CD8A, GATA3, HOXD10, MYO7A, OSR2, PLCB1, and SPOCK2) significantly upregulated in PVL compared to control and 5 genes (ANKRD6, DLG2, GPX3, PITX2, and ZNF736) significantly downregulated. The status of de-regulation found for PVL patients was concordant with what was found for OSCC samples compared to normal adjacent tissue.& nbsp; Conclusion: Our findings show the potential of methylation markers in PVL and suggest novel OSCC diagnostic biomarkers which may boost the development of novel epigenetic-based therapies.

yearjournalcountryeditionlanguage
2021-01-01
https://fundanet.cipf.es/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=3749