| Texto completo | |
| Autor(es): Mostrar menos - |
Bueno, Ana Carolina
;
Stecchini, Monica F.
;
Marrero-Gutierrez, Junier
;
More, Candy Bellido
;
Leal, Leticia Ferro
;
Gomes, Debora Cristiane
;
de Lima Neto, Daniel Ferreira
;
Brandalise, Silvia Regina
;
Cardinalli, Izilda Aparecida
;
Yunes, Jose Andres
;
Junqueira, Thais
;
Scrideli, Carlos Alberto
;
Fernandes Molina, Carlos Augusto
;
Ramalho, Fernando Silva
;
Tucci, Silvio
;
Coeli-Lacchini, Fernanda Borchers
;
Moreira, Ayrton Custodio
;
Ramalho, Leandra
;
Nicoliello Vencio, Ricardo Zorzetto
;
De Castro, Margaret
;
Antonini, Sonir Roberto R.
Número total de Autores: 21
|
| Tipo de documento: | Artigo Científico |
| Fonte: | EUROPEAN JOURNAL OF ENDOCRINOLOGY; v. 186, n. 5, p. 13-pg., 2022-05-01. |
| Resumo | |
Objective: Pediatric adrenocortical tumors (pACT) display complex genomic backgrounds, lacking robust prognostic markers and targeted therapeutic options. Vitamin D-3 receptor (VDR) promoter hypermethylation and underexpression were reported in adrenocortical carcinomas from adult patients. In this study, we aimed to investigate VDR expression levels and methylation status in pACT and their clinical and prognostic significance. Design: Retrospective cross-sectional study enrolling pediatric patients with ACT from two tertiary referral institutions. Methods: We evaluated clinicopathological features, VDR mRNA (qPCR) and protein (immunohistochemistry) expression, and VDR-wide methylation of ACT samples from 108 pediatric patients. Fourteen pediatric and 32 fetal and postnatal normal adrenals were used as controls. Results: Unlike in pre- and post-natal normal adrenals, most pACT lacked nuclear VDR expression and had reduced mRNA levels, especially the carcinomas. Unsupervised analysis of VDR methylation data revealed two groups of pACT with distinct disease features and outcomes. Tumors with high VDR methylation presented lower mRNA levels, and the respective patients presented advanced disease and reduced disease-free and overall survival. Conclusions: VDR has a role in normal adrenocortical development and homeostasis, which is impaired during tumorigenesis. VDR hypermethylation and underexpression may be both predictive and prognostic biomarkers for pACT. (AU) | |
| Processo FAPESP: | 15/19663-5 - Investigação das bases moleculares da tumorigênese adrenocortical e busca por novos alvos terapêuticos |
| Beneficiário: | Sonir Roberto Rauber Antonini |
| Modalidade de apoio: | Auxílio à Pesquisa - Regular |
| Processo FAPESP: | 20/03835-0 - Aplicação de protocolos padrão de Inteligência Artifical na transcritômica de tumores adrenocorticais pediátricos para estratificação e busca de biomarcadores |
| Beneficiário: | Junier Marrero Gutiérrez |
| Modalidade de apoio: | Bolsas no Brasil - Programa Capacitação - Treinamento Técnico |
| Processo FAPESP: | 14/03989-6 - Mecanismos fisiopatológicos e moleculares de tumorigênese: abordagem baseada em plataformas de sequenciamento em escala genômica (NGS - Next-Generation Sequencing) |
| Beneficiário: | Margaret de Castro |
| Modalidade de apoio: | Auxílio à Pesquisa - Temático |
| Processo FAPESP: | 19/00860-6 - Mecanismos fisiopatológicos e moleculares de tumorigênese: abordagem baseada em plataformas de sequenciamento em escala genômica (NGS - Next-generation sequencing). |
| Beneficiário: | Ana Carolina Bueno de Queiroz Arruda |
| Modalidade de apoio: | Bolsas no Brasil - Pós-Doutorado |