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1.
Epigenomics ; 13(2): 113-127, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33351665

RESUMO

Aims:PD-1 expression is associated with DNA methylation in head and neck squamous cell carcinomas (HNSCCs). We performed methylation analysis at single CpG site resolution in order to understand epigenetic regulation. Materials and methods: CpG methylation analysis of PD-1 and long non-coding RNA (lncRNA) AC131097.3 was performed in n = 528 HNSCCs and n = 50 normal adjacent tissues provided by The Cancer Genome Atlas and in isolated leukocytes. Results:PD-1 mRNA and AC131097.3 lncRNA expression correlated inversely with promoter and positively with gene body CpG methylation. PD-1 and AC131097.3 are co-expressed. Methylation was sequence-contextually associated with human papillomavirus prognosis, mutational load, and immune infiltrates. Conclusions: The significance of PD-1 and AC131097.3 methylation is highly sequence-contextual. AC131097.3 might play a role in HNSCC.


Assuntos
Carcinoma de Células Escamosas/genética , Metilação de DNA/genética , Neoplasias de Cabeça e Pescoço/genética , Receptor de Morte Celular Programada 1/genética , RNA Longo não Codificante/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Biomarcadores Tumorais/genética , Epigênese Genética/genética , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Prognóstico , Regiões Promotoras Genéticas/genética
2.
Immunotherapy ; 12(12): 903-920, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32684057

RESUMO

Aim: We investigated DNA methylation patterns of immune checkpoint genes PD-1, PD-L1, PD-L2, CTLA4 and an adjacent long noncoding RNA in papillary thyroid carcinoma (PTC). Materials & methods: DNA methylation and mRNA expression were examined in PTCs. DNA methylation was correlated with mRNA expression, BRAF and RAS mutational status, and immune cell infiltration. Results: Inverse correlations between DNA methylation and mRNA expression were observed. Immune checkpoint expression correlated positively, and DNA methylation negatively, with immune cell infiltration. Higher DNA methylation levels accompanied by lower immune checkpoint expression were observed in RAS-mutated tumors. Conclusion: We suggest epigenetic regulation of immune checkpoints in PTC. Methylation was associated with BRAF and RAS mutation status. DNA methylation might be a promising biomarker candidate in the context of immunotherapies in PTC.


Assuntos
Antígeno B7-H1/genética , Antígeno CTLA-4/genética , Metilação de DNA/genética , Proteína 2 Ligante de Morte Celular Programada 1/genética , Receptor de Morte Celular Programada 1/genética , Câncer Papilífero da Tireoide/genética , Neoplasias da Glândula Tireoide/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígeno B7-H1/imunologia , Antígeno CTLA-4/imunologia , Estudos de Coortes , Metilação de DNA/imunologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteína 2 Ligante de Morte Celular Programada 1/imunologia , Receptor de Morte Celular Programada 1/imunologia , Estudos Retrospectivos , Câncer Papilífero da Tireoide/imunologia , Neoplasias da Glândula Tireoide/imunologia , Adulto Jovem
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