{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T16:12:42Z","timestamp":1790611962404,"version":"4.1.0"},"reference-count":77,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,1,15]],"date-time":"2025-01-15T00:00:00Z","timestamp":1736899200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"MEAE AMBASS FRANCE AU PEROU FSPI","award":["S-AC23007"],"award-info":[{"award-number":["S-AC23007"]}]},{"name":"Fili\u00e8re Sant\u00e9 Maladie Rare du Foie de l\u2019Adulte et de l\u2019Enfant","award":["S-AC23007"],"award-info":[{"award-number":["S-AC23007"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Medulloblastoma (MB) is the most common malignant brain tumor in children, typically arising during infancy and childhood. Despite multimodal therapies achieving a response rate of 70% in children older than 3 years, treatment remains challenging. Ferroptosis, a form of regulated cell death, can be induced in medulloblastoma cells in vitro using erastin or RSL3. Using two independent medulloblastoma RNA-sequencing cohorts (MB-PBTA and MTAB-10767), we investigated the expression of ferroptosis-related molecules through multiple approaches, including Weighted Gene Co-Expression Network Analysis (WGCNA), molecular subtype stratification, protein\u2013protein interaction (PPI) networks, and univariable and multivariable overall survival analyses. A prognostic expression score was computed based on a cross-validated ferroptosis signature. In training and validation cohorts, the regulation of the ferroptosis transcriptional program distinguished the four molecular subtypes of medulloblastoma. WGCNA identified nine gene modules in the MB tumor transcriptome; five correlated with molecular subtypes, implicating pathways related to oxidative stress, hypoxia, and trans-synaptic signaling. One module, associated with disease recurrence, included epigenetic regulators and nucleosome organizers. Univariable survival analyses identified a 45-gene ferroptosis prognostic signature associated with nutrient sensing, cysteine and methionine metabolism, and trans-sulfuration within a one-carbon metabolism. The top ten unfavorable ferroptosis genes included CCT3, SNX5, SQOR, G3BP1, CARS1, SLC39A14, FAM98A, FXR1, TFAP2C, and ATF4. Patients with a high ferroptosis score showed a worse prognosis, particularly in the G3 and SHH subtypes. The PPI network highlighted IL6 and CBS as unfavorable hub genes. In a multivariable overall survival model, which included gender, age, and the molecular subtype classification, the ferroptosis expression score was validated as an independent adverse prognostic marker (hazard ratio: 5.8; p-value = 1.04 \u00d7 10\u22129). This study demonstrates that the regulation of the ferroptosis transcriptional program is linked to medulloblastoma molecular subtypes and patient prognosis. A cross-validated ferroptosis signature was identified in two independent RNA-sequencing cohorts, and the ferroptosis score was confirmed as an independent and adverse prognostic factor in medulloblastoma.<\/jats:p>","DOI":"10.3390\/antiox14010096","type":"journal-article","created":{"date-parts":[[2025,1,15]],"date-time":"2025-01-15T10:00:01Z","timestamp":1736935201000},"page":"96","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Ferroptosis Transcriptional Regulation and Prognostic Impact in Medulloblastoma Subtypes Revealed by RNA-Seq"],"prefix":"10.3390","volume":"14","author":[{"given":"Christophe","family":"Desterke","sequence":"first","affiliation":[{"name":"INSERM UMRS-1310, Facult\u00e9 de M\u00e9decine du Kremlin Bic\u00eatre, Universit\u00e9 Paris-Saclay, F-94270 Le Kremlin-Bic\u00eatre, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2226-8230","authenticated-orcid":false,"given":"Yuanji","family":"Fu","sequence":"additional","affiliation":[{"name":"INSERM, CNRS, Institut Necker Enfants Malades, Universit\u00e9 Paris Cit\u00e9, F-75015 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0798-7544","authenticated-orcid":false,"given":"Jenny","family":"Bonifacio-Mundaca","sequence":"additional","affiliation":[{"name":"National Tumor Bank, Department of Pathology, National Institute of Neoplastic Diseases, Surquillo 15038, Peru"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1215-5857","authenticated-orcid":false,"given":"Claudia","family":"Monge","sequence":"additional","affiliation":[{"name":"Unit\u00e9 Organisation Nucl\u00e9aire et Oncogen\u00e8se, Institut Pasteur, Universit\u00e9 Paris Cit\u00e9, INSERM U993, F-75015 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9407-1592","authenticated-orcid":false,"given":"Pascal","family":"Pineau","sequence":"additional","affiliation":[{"name":"Unit\u00e9 Organisation Nucl\u00e9aire et Oncogen\u00e8se, Institut Pasteur, Universit\u00e9 Paris Cit\u00e9, INSERM U993, F-75015 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-5726-8814","authenticated-orcid":false,"given":"Jorge","family":"Mata-Garrido","sequence":"additional","affiliation":[{"name":"Unit\u00e9 Organisation Nucl\u00e9aire et Oncogen\u00e8se, Institut Pasteur, Universit\u00e9 Paris Cit\u00e9, INSERM U993, F-75015 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1428-4852","authenticated-orcid":false,"given":"Raquel","family":"Franc\u00e9s","sequence":"additional","affiliation":[{"name":"Energy & Memory, Brain Plasticity Unit, CNRS, ESPCI Paris, PSL Research University, F-75006 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1038\/nrclinonc.2014.181","article-title":"Medulloblastoma\u2014Translating Discoveries from the Bench to the Bedside","volume":"11","author":"Gajjar","year":"2014","journal-title":"Nat. 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