DNA methylation-based depiction of the immune microenvironment and immune-associated long non-coding RNAs in oral cavity squamous cell carcinomas
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Citações na Scopus
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Tipo de produção
article
Data de publicação
2023
Título da Revista
ISSN da Revista
Título do Volume
Editora
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
Autores
CALANCA, Naiade
FRANCISCO, Ana Lucia Noronha
BIZINELLI, Daniela
KUASNE, Hellen
BARROS FILHO, Mateus Camargo
FLORES, Bianca Campos Troncarelli
PINTO, Clovis Antonio Lopes
RAINHO, Claudia Aparecida
SOARES, Milena Botelho Pereira
Citação
BIOMEDICINE & PHARMACOTHERAPY, v.167, article ID 115559, 14p, 2023
Resumo
Oral cavity squamous cell carcinoma (OSCC) is a complex and dynamic disease characterized by clinicopathological and molecular heterogeneity. Spatial and temporal heterogeneity of cell subpopulations has been associated with cancer progression and implicated in the prognosis and therapy response. Emerging evidence indicates that aberrant epigenetic profiles in OSCC may foster an immunosuppressive tumor microenvironment by modulating the expression of immune-related long non-coding RNAs (lncRNAs). DNA methylation analysis was performed in 46 matched OSCC and normal adjacent tissue samples using a genome-wide platform (Infinium HumanMethylation450 BeadChip). Reference-based computational deconvolution (MethylCIBERSORT) was applied to infer the immune cell composition of the bulk samples. The expression levels of genes encoding immune markers and differentially methylated lncRNAs were investigated using The Cancer Genome Atlas dataset. OSCC specimens presented distinct immune cell composition, including the enrichment of monocyte lineage cells, natural killer cells, cytotoxic T-lymphocytes, regulatory T-lymphocytes, and neutrophils. In contrast, B-lymphocytes, effector T-lymphocytes, and fibroblasts were diminished in tumor samples. The hypomethylation of three immune-associated lncRNAs (MEG3, MIR155HG, and WFDC21P) at individual CpG sites was confirmed by bisulfite-pyrosequencing. Also, the upregulation of a set of immune markers (FOXP3, GZMB, IL10, IL2RA, TGFB, IFNG, TDO2, IDO1, and HIF1A) was detected. The immune cell composition, immune markers alteration, and dysregulation of immune-associated lncRNAs reinforce the impact of the immune microenvironment in OSCC. These concurrent factors contribute to tumor heterogeneity, suggesting that epiimmunotherapy could be an efficient alternative to treat OSCC.
Palavras-chave
Oral cancer, Tumor immune microenvironment, LncRNAs, DNA methylation, Deconvolution
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Coleções
Artigos e Materiais de Revistas Científicas - FM/MCG
Artigos e Materiais de Revistas Científicas - HC/ICESP
Artigos e Materiais de Revistas Científicas - HC/ICHC
Artigos e Materiais de Revistas Científicas - LIM/03
Artigos e Materiais de Revistas Científicas - LIM/28
Artigos e Materiais de Revistas Científicas - ODS/03
Artigos e Materiais de Revistas Científicas - HC/ICESP
Artigos e Materiais de Revistas Científicas - HC/ICHC
Artigos e Materiais de Revistas Científicas - LIM/03
Artigos e Materiais de Revistas Científicas - LIM/28
Artigos e Materiais de Revistas Científicas - ODS/03