{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T09:39:49Z","timestamp":1778665189266,"version":"3.51.4"},"reference-count":52,"publisher":"Oxford University Press (OUP)","issue":"5","content-domain":{"domain":["eje.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,5,1]]},"abstract":"<jats:sec>\n<jats:title>Objective<\/jats:title>\n<jats:p>Pediatric adrenocortical tumors (pACT) display complex genomic backgrounds, lacking robust prognostic markers and targeted therapeutic options. Vitamin D<jats:sub>3<\/jats:sub> 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.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Design<\/jats:title>\n<jats:p>Retrospective cross-sectional study enrolling pediatric patients with ACT from two tertiary referral institutions.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Methods<\/jats:title>\n<jats:p>We evaluated clinicopathological features, VDR mRNA (qPCR) and protein (immunohistochemistry) expression, and <jats:italic>VDR<\/jats:italic>-wide methylation of ACT samples from 108 pediatric patients. Fourteen pediatric and 32 fetal and postnatal normal adrenals were used as controls.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>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 <jats:italic>VDR<\/jats:italic> methylation data revealed two groups of pACT with distinct disease features and outcomes. Tumors with high <jats:italic>VDR<\/jats:italic> methylation presented lower mRNA levels, and the respective patients presented advanced disease and reduced disease-free and overall survival.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Conclusions<\/jats:title>\n<jats:p>VDR has a role in normal adrenocortical development and homeostasis, which is impaired during tumorigenesis. <jats:italic>VDR<\/jats:italic> hypermethylation and underexpression may be both predictive and prognostic biomarkers for pACT.<\/jats:p>\n<\/jats:sec>","DOI":"10.1530\/eje-21-0879","type":"journal-article","created":{"date-parts":[[2022,3,15]],"date-time":"2022-03-15T14:45:42Z","timestamp":1647355542000},"page":"573-585","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-7","source":"Crossref","is-referenced-by-count":9,"title":["Vitamin D receptor hypermethylation as a biomarker for pediatric adrenocortical tumors"],"prefix":"10.1093","volume":"186","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9043-9831","authenticated-orcid":true,"given":"Ana Carolina","family":"Bueno","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M\u00f4nica F","family":"Stecchini","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junier","family":"Marrero-Guti\u00e9rrez","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Candy Bellido","family":"More","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leticia Ferro","family":"Leal","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D\u00e9bora Cristiane","family":"Gomes","sequence":"additional","affiliation":[{"name":"Federal University of Uberlandia, Uberlandia, Minas Gerais, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel Ferreira","family":"de Lima Neto","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvia Regina","family":"Brandalise","sequence":"additional","affiliation":[{"name":"Boldrini Children\u2019s Center, State University of Campinas, Campinas, Sao Paulo, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Izilda Aparecida","family":"Cardinalli","sequence":"additional","affiliation":[{"name":"Boldrini Children\u2019s Center, State University of Campinas, Campinas, Sao Paulo, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9 Andres","family":"Yunes","sequence":"additional","affiliation":[{"name":"Boldrini Children\u2019s Center, State University of Campinas, Campinas, Sao Paulo, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thais","family":"Junqueira","sequence":"additional","affiliation":[{"name":"Boldrini Children\u2019s Center, State University of Campinas, Campinas, Sao Paulo, 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