{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T13:18:19Z","timestamp":1790774299490,"version":"4.1.0"},"reference-count":42,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T00:00:00Z","timestamp":1776729600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Glioblastoma (GBM) is characterized by hypoxia-driven metabolic adaptation and profound therapeutic resistance. Ferroptosis, an iron-dependent lipid peroxidation-related cell death process, has emerged as a potential vulnerability; however, its relationship with hypoxia signaling remains incompletely defined. In this study, we performed integrative transcriptomic and single-cell RNA sequencing analyses to investigate the relationship between hypoxia signaling and ferroptosis-related gene signatures in GBM. Intersection analysis of hypoxia-associated differentially expressed genes and curated ferroptosis-related gene sets identified 29 core candidate genes. FerroScore stratification revealed that tumors with higher ferroptosis-related transcriptional signatures were significantly associated with poor overall survival. Among these genes, HILPDA emerged as a hypoxia-associated gene consistently linked to ferroptosis-related gene expression patterns and immune-related transcriptional programs. HILPDA expression showed significant correlations with iron-ROS axis components, including HMOX1, NOX4, and STEAP3, and was associated with immune microenvironment changes characterized by T cell depletion and inflammatory infiltration. Single-cell RNA-seq analysis further supported the cellular-level association between HILPDA expression and hypoxia-related transcriptional states. Structural equation modeling suggested that the relationship between HILPDA expression and ferroptosis-related gene signatures may be mediated through hypoxia-related pathways. Collectively, these findings indicate a transcriptomic association between hypoxia signaling and ferroptosis-related gene signatures in GBM and identify HILPDA as a candidate gene associated with this axis.<\/jats:p>","DOI":"10.3390\/ijms27083698","type":"journal-article","created":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T16:10:44Z","timestamp":1776787844000},"page":"3698","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Integrated Transcriptomic and Single-Cell Analyses Identify HILPDA as a Hypoxia-Mediated Regulator of Ferroptotic Signaling in Glioblastoma"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7884-7971","authenticated-orcid":false,"given":"Nelin","family":"Hacioglu","sequence":"first","affiliation":[{"name":"Department of Molecular Biology and Genetics, Faculty of Science and Literature, Balikesir University, \u00c7agis Campus, Balikesir 10100, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"iii1","DOI":"10.1093\/neuonc\/noac161","article-title":"CBTRUS Statistical Report: Pediatric Brain Tumor Foundation Childhood and Adolescent Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2014\u20132018","volume":"24","author":"Ostrom","year":"2022","journal-title":"Neuro-Oncology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1093\/neuonc\/noab106","article-title":"The 2021 WHO Classification of Tumors of the Central Nervous System: A summary","volume":"23","author":"Louis","year":"2021","journal-title":"Neuro-Oncology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"418","DOI":"10.3892\/ol.2024.14551","article-title":"Temozolomide based treatment in glioblastoma: 6 vs. 12 months","volume":"28","author":"Fasano","year":"2024","journal-title":"Oncol. 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