Prognostic significance of SLC25A28 and its associations with mitochondrial metabolism and immune features in glioma
Abstract
BackgroundSLC25A28 encodes the mitochondrial iron transporter mitoferrin-2, but its prognostic relevance and biological associations in glioma remain incompletely characterized. We investigated its clinical significance and relationships with metabolic, ferroptosis-related and immune features across glioma cohorts.MethodsSLC25-family genes were screened in CGGA and TCGA, followed by survival analysis and meta-analysis across nine GlioVis cohorts. Clinical Cox models, prognostic scores and grade/IDH subgroups were evaluated. Metabolic, immune and curated ferroptosis-related signatures were examined using clinically adjusted models, and immune-cell and checkpoint analyses underwent false-discovery-rate correction. SLC25A28 expression was assessed by qRT-PCR and Western blotting.ResultsLower SLC25A28 expression was associated with unfavorable clinicopathological features and shorter overall survival (pooled hazard ratio, 1.91; 95% confidence interval, 1.46–2.50; I² = 84.9%). Exploratory analyses supported survival associations in both IDH-mutant and IDH-wild-type subgroups of CGGA and TCGA, although findings within glioblastoma varied. Positive oxidative-phosphorylation associations persisted after grade/IDH adjustment in both pooled cohorts; within glioblastoma, this association was supported in CGGA but not TCGA. Ferroptosis-related transcriptional associations were also detected, with consistent all-glioma WikiPathways results across sensitivity analyses in TCGA but scoring-method and cohort dependence in regulator signatures. Immune-cell differences survived correction for 10 of 22 populations in CGGA and 16 of 22 in TCGA, and three checkpoint genes showed positive correlations in both cohorts. qRT-PCR and Western blotting confirmed lower SLC25A28 expression in U87 and U251 cells than in normal human astrocytes.ConclusionsSLC25A28 is a candidate prognostic biomarker associated with mitochondrial metabolism, ferroptosis-related transcriptional features and immune features in glioma. Multi-cohort survival evidence and clinically adjusted molecular associations support further evaluation of its prognostic and biological relevance. Subtype-specific clinical validation and functional investigations will help define its clinical utility and biological role.
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BibTeX
@article{yu2026prognostic,
title = {{Prognostic significance of SLC25A28 and its associations with mitochondrial metabolism and immune features in glioma}},
author = {Wangyang Yu and Yue Yang and Wenli Guo and Yafeng Wang and Jinsong Bai and Chen Li},
journal = {Frontiers in Oncology},
year = {2026},
month = oct,
doi = {10.3389/fonc.2026.1917001},
url = {https://www.frontiersin.org/articles/10.3389/fonc.2026.1917001},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Prognostic significance of SLC25A28 and its associations with mitochondrial metabolism and immune features in glioma
AU - Wangyang Yu
AU - Yue Yang
AU - Wenli Guo
AU - Yafeng Wang
AU - Jinsong Bai
AU - Chen Li
PY - 2026
DA - 2026/10/30
JO - Frontiers in Oncology
DO - 10.3389/fonc.2026.1917001
UR - https://www.frontiersin.org/articles/10.3389/fonc.2026.1917001
AB - BackgroundSLC25A28 encodes the mitochondrial iron transporter mitoferrin-2, but its prognostic relevance and biological associations in glioma remain incompletely characterized. We investigated its clinical significance and relationships with metabolic, ferroptosis-related and immune features across glioma cohorts.MethodsSLC25-family genes were screened in CGGA and TCGA, followed by survival analysis and meta-analysis across nine GlioVis cohorts. Clinical Cox models, prognostic scores and grade/IDH subgroups were evaluated. Metabolic, immune and curated ferroptosis-related signatures were examined using clinically adjusted models, and immune-cell and checkpoint analyses underwent false-discovery-rate correction. SLC25A28 expression was assessed by qRT-PCR and Western blotting.ResultsLower SLC25A28 expression was associated with unfavorable clinicopathological features and shorter overall survival (pooled hazard ratio, 1.91; 95% confidence interval, 1.46–2.50; I² = 84.9%). Exploratory analyses supported survival associations in both IDH-mutant and IDH-wild-type subgroups of CGGA and TCGA, although findings within glioblastoma varied. Positive oxidative-phosphorylation associations persisted after grade/IDH adjustment in both pooled cohorts; within glioblastoma, this association was supported in CGGA but not TCGA. Ferroptosis-related transcriptional associations were also detected, with consistent all-glioma WikiPathways results across sensitivity analyses in TCGA but scoring-method and cohort dependence in regulator signatures. Immune-cell differences survived correction for 10 of 22 populations in CGGA and 16 of 22 in TCGA, and three checkpoint genes showed positive correlations in both cohorts. qRT-PCR and Western blotting confirmed lower SLC25A28 expression in U87 and U251 cells than in normal human astrocytes.ConclusionsSLC25A28 is a candidate prognostic biomarker associated with mitochondrial metabolism, ferroptosis-related transcriptional features and immune features in glioma. Multi-cohort survival evidence and clinically adjusted molecular associations support further evaluation of its prognostic and biological relevance. Subtype-specific clinical validation and functional investigations will help define its clinical utility and biological role.
SN - 2234-943X
ER -