ArticleDiscover oncology2025
Transcriptomic HEPN1 signatures predict treatment response in low grade glioma.
Article in Discover oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundIron-dependent ferroptosis emerges as a promising therapeutic avenue for glioma treatment, with ferroptosis-related genes such as HEPN1 offering potential as critical biomarkers when analyzed at single-cell resolution. By leveraging comprehensive single-cell transcriptomic approaches, this investigation seeks to establish HEPN1 as a pivotal biomarker while examining its utility in directing ferroptosis-targeted therapeutic interventions for glioma patients.
methodWe retrieved glioma gene expression datasets from TCGA and GEO repositories for analysis. Through WGCNA methodology, we constructed gene co-expression networks to pinpoint ferroptosis-associated gene modules. Comprehensive single-cell RNA sequencing analysis enabled characterization of expression patterns and cellular heterogeneity among ferroptosis-related genes spanning multiple cell types. We performed differential expression analysis to detect ferroptosis-related genes with significant expression across distinct cellular populations. Characterization of cell-type-specific expression profiles revealed ferroptosis pathway activation patterns, while core gene validation utilized GL261 and BV2 cell line experiments.
resultMultiple ferroptosis-related gene modules emerged from WGCNA analysis, with one module demonstrating significant correlation with glioma clinical characteristics and patient prognosis. Distinct expression patterns and cellular distribution of key ferroptosis genes across various cell types within the glioma microenvironment were revealed through single-cell sequencing. Complex inter-cellular interactions within ferroptosis signaling pathways were demonstrated by network analysis. Cell-type-specific analysis revealed elevated expression of HEPN1, SOX2, OLIG2, and PTPRZ1 in GL261 cells relative to BV2 cells, indicating their potential as prognostic biomarkers for glioma therapeutic outcomes.
conclusionThe system elucidates the mechanism of iron death related genes in glioma heterogeneity, providing an important theoretical basis for precise treatment of gliomas.
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