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Bueno, Ana Carolina; Stecchini, Mônica F; Marrero-Gutiérrez, Junier; More, Candy Bellido; Leal, Leticia Ferro; Gomes, Débora Cristiane; de Lima Neto, Daniel Ferreira; Brandalise, Silvia Regina; Cardinalli, Izilda Aparecida; Yunes, José Andres; Junqueira, Thais; Scrideli, Carlos Alberto; Molina, Carlos Augusto Fernandes; Ramalho, Fernando Silva; Tucci, Silvio; Coeli-Lacchini, Fernanda Borchers; Moreira, Ayrton Custodio; Ramalho, Leandra; Vêncio, Ricardo Zorzetto Nicoliello; De Castro, Margaret; Antonini, Sonir Roberto R
European Journal of Endocrinology, 04/2022, Letnik: 186, Številka: 5Journal Article
Objective Pediatric adrenocortical tumors (pACT) display complex genomic backgrounds, lacking robust prognostic markers and targeted therapeutic options. Vitamin D3 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.
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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Povezave do osebnih bibliografij avtorjev | Povezave do podatkov o raziskovalcih v sistemu SICRIS |
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Vir: Osebne bibliografije
in: SICRIS
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