Multi-omics landscape of alternative splicing in diffuse midline glioma reveals immune- and neural-driven subtypes with implications for spliceosome-targeted therapy DOI Creative Commons

Chaxian Liu,

Yue Liu, Hao Lin

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: April 16, 2025

Introduction H3K27-altered diffuse midline glioma (DMG) is a highly aggressive subtype, accounting for approximately 60% of pediatric high-grade gliomas, with median survival less than 12 months. Due to its predominant localization in the brainstem, conventional surgical resection often unfeasible, underscoring urgent need alternative therapeutic strategies. While previous studies on DMG have primarily focused regulatory mechanisms at protein level, role splicing remains largely unexplored. Given potential impact gene regulation and tumor progression, comprehensive analysis could provide novel insights into targeted or immune strategies, complementing existing transcriptomic DMG. Methods To investigate landscape DMG, we performed transcriptome sequencing (RNA-seq) patient-derived H3WT cell lines, integrating these data RNA-seq single-cell (scRNA-seq) datasets from published sources. This approach enabled us delineate validate distinct features cellular level. Results Our multi-omics revealed significant transcriptional alterations compared particularly pathways related neuro-regulation, metabolism, immunity. Further in-depth identified extensive changes predominantly associated RNA modifications key extracellular matrix nucleotide metabolism. Integrating findings, characterized five RNA-associated proteins that binary classification neural subtypes, each subtype exhibiting prognostic features. Notably, RALYL as regulator progression. Discussion findings indicate exhibits alterations, which play crucial roles tumorigenesis Additionally, our study an RNA-binding protein-based factor, highlighting target.

Language: Английский

Multi-omics landscape of alternative splicing in diffuse midline glioma reveals immune- and neural-driven subtypes with implications for spliceosome-targeted therapy DOI Creative Commons

Chaxian Liu,

Yue Liu, Hao Lin

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: April 16, 2025

Introduction H3K27-altered diffuse midline glioma (DMG) is a highly aggressive subtype, accounting for approximately 60% of pediatric high-grade gliomas, with median survival less than 12 months. Due to its predominant localization in the brainstem, conventional surgical resection often unfeasible, underscoring urgent need alternative therapeutic strategies. While previous studies on DMG have primarily focused regulatory mechanisms at protein level, role splicing remains largely unexplored. Given potential impact gene regulation and tumor progression, comprehensive analysis could provide novel insights into targeted or immune strategies, complementing existing transcriptomic DMG. Methods To investigate landscape DMG, we performed transcriptome sequencing (RNA-seq) patient-derived H3WT cell lines, integrating these data RNA-seq single-cell (scRNA-seq) datasets from published sources. This approach enabled us delineate validate distinct features cellular level. Results Our multi-omics revealed significant transcriptional alterations compared particularly pathways related neuro-regulation, metabolism, immunity. Further in-depth identified extensive changes predominantly associated RNA modifications key extracellular matrix nucleotide metabolism. Integrating findings, characterized five RNA-associated proteins that binary classification neural subtypes, each subtype exhibiting prognostic features. Notably, RALYL as regulator progression. Discussion findings indicate exhibits alterations, which play crucial roles tumorigenesis Additionally, our study an RNA-binding protein-based factor, highlighting target.

Language: Английский

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