转录组学HEPN1特征可预测低级别胶质瘤的治疗反应。

Transcriptomic HEPN1 signatures predict treatment response in low grade glioma.

作者信息

Jiao Lei, Fang Shuhua, Zhang Jianbo

机构信息

Nanjing Lishui People's Hospital, No.86 Chong Wen road, Lishui District, Nanjing City, 211299, Jiangsu Province, China.

出版信息

Discov Oncol. 2025 Aug 15;16(1):1561. doi: 10.1007/s12672-025-03395-1.

DOI:10.1007/s12672-025-03395-1

PMID:40815398

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.

摘要

背景

铁依赖性铁死亡成为一种有前景的胶质瘤治疗途径，当以单细胞分辨率进行分析时，诸如HEPN1等铁死亡相关基因具有作为关键生物标志物的潜力。通过利用全面的单细胞转录组学方法，本研究旨在确立HEPN1作为关键生物标志物，同时检验其在指导针对胶质瘤患者的铁死亡靶向治疗干预中的效用。

方法

我们从TCGA和GEO数据库中检索胶质瘤基因表达数据集进行分析。通过加权基因共表达网络分析（WGCNA）方法，我们构建基因共表达网络以确定铁死亡相关基因模块。全面的单细胞RNA测序分析能够表征多种细胞类型中铁死亡相关基因的表达模式和细胞异质性。我们进行差异表达分析以检测在不同细胞群体中具有显著表达的铁死亡相关基因。细胞类型特异性表达谱的表征揭示了铁死亡途径激活模式，而核心基因验证利用GL261和BV2细胞系实验。

结果

WGCNA分析产生了多个铁死亡相关基因模块，其中一个模块与胶质瘤临床特征和患者预后显示出显著相关性。通过单细胞测序揭示了胶质瘤微环境中各种细胞类型间关键铁死亡基因的不同表达模式和细胞分布。网络分析证明了铁死亡信号通路内复杂的细胞间相互作用。细胞类型特异性分析显示，相对于BV2细胞，GL261细胞中HEPN1、SOX2、OLIG2和PTPRZ1的表达升高，表明它们作为胶质瘤治疗结果预后生物标志物的潜力。