Transcriptomic HEPN1 signatures predict treatment response in low grade glioma

Abstract Background Iron-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 approa...

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Main Authors: Lei Jiao, Shuhua Fang, Jianbo Zhang
Format: Article
Language:English
Published: Springer 2025-08-01
Series:Discover Oncology
Subjects:
Online Access:https://doi.org/10.1007/s12672-025-03395-1
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author Lei Jiao
Shuhua Fang
Jianbo Zhang
author_facet Lei Jiao
Shuhua Fang
Jianbo Zhang
author_sort Lei Jiao
collection DOAJ
description Abstract Background Iron-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. Method We 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. Result Multiple 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. Conclusion The 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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spelling doaj-art-091f97d8c18341abba938205bbc16b892025-08-20T04:02:56ZengSpringerDiscover Oncology2730-60112025-08-0116111510.1007/s12672-025-03395-1Transcriptomic HEPN1 signatures predict treatment response in low grade gliomaLei Jiao0Shuhua Fang1Jianbo Zhang2Nanjing Lishui People’s HospitalNanjing Lishui People’s HospitalNanjing Lishui People’s HospitalAbstract Background Iron-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. Method We 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. Result Multiple 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. Conclusion The system elucidates the mechanism of iron death related genes in glioma heterogeneity, providing an important theoretical basis for precise treatment of gliomas.https://doi.org/10.1007/s12672-025-03395-1HEPN1FerroptosisSingle-cell RNA sequencingLow-grade gliomaBiomarker
spellingShingle Lei Jiao
Shuhua Fang
Jianbo Zhang
Transcriptomic HEPN1 signatures predict treatment response in low grade glioma
Discover Oncology
HEPN1
Ferroptosis
Single-cell RNA sequencing
Low-grade glioma
Biomarker
title Transcriptomic HEPN1 signatures predict treatment response in low grade glioma
title_full Transcriptomic HEPN1 signatures predict treatment response in low grade glioma
title_fullStr Transcriptomic HEPN1 signatures predict treatment response in low grade glioma
title_full_unstemmed Transcriptomic HEPN1 signatures predict treatment response in low grade glioma
title_short Transcriptomic HEPN1 signatures predict treatment response in low grade glioma
title_sort transcriptomic hepn1 signatures predict treatment response in low grade glioma
topic HEPN1
Ferroptosis
Single-cell RNA sequencing
Low-grade glioma
Biomarker
url https://doi.org/10.1007/s12672-025-03395-1
work_keys_str_mv AT leijiao transcriptomichepn1signaturespredicttreatmentresponseinlowgradeglioma
AT shuhuafang transcriptomichepn1signaturespredicttreatmentresponseinlowgradeglioma
AT jianbozhang transcriptomichepn1signaturespredicttreatmentresponseinlowgradeglioma