Distinct spatial N-glycan profiles reveal glioblastoma-specific signatures.

IF 5.6 2区医学 Q1 ONCOLOGY

The Journal of Pathology Pub Date : 2025-02-19 DOI:10.1002/path.6401

Aaron O Angerstein, Lyndsay E A Young, Thatchawan Thanasupawat, Jerry Vriend, Grace Grimsley, Xueqing Lun, Donna L Senger, Namita Sinha, Jason Beiko, Marshall Pitz, Sabine Hombach-Klonisch, Richard R Drake, Thomas Klonisch

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引用次数: 0

Abstract

This study explored the complex interactions between glycosylation patterns, tumour biology, and therapeutic responses to temozolomide (TMZ) in human malignant glioma, specifically CNS WHO grade 3 oligodendroglioma (ODG) and glioblastoma (GB). Using spatial imaging of N-glycans in formalin-fixed paraffin-embedded (FFPE) tissue sections via MALDI-MSI, we analysed the N-glycome in primary and recurrent GB tissues and orthotopic xenografts of patient-derived brain tumour-initiating cells (BTIC) sensitive or resistant to TMZ. We identified unique N-glycosylation profiles, with nontumor brain (NTB) and ODG showing higher levels of bisecting and tri-antennary structures, while GB exhibited more tetra-antennary and sialylated N-glycans. Distinctive sialylation patterns were observed, with specific α2,6 and α2,3 isomeric linkages significantly altered in GB. Moreover, comparative analysis of primary and recurrent GB tissues revealed elevated high mannose N-glycans in primary GB and fucosylated bi- and tri-antennary N-glycans in recurrent GB tissues. Next, in the orthotopic xenografts of TMZ-sensitive and TMZ-resistant patient brain tumour initiating cells (BTIC), we identified potential N-glycan markers for TMZ treatment response and resistance. Finally, we found significantly altered expression of genes involved in N-glycan biosynthesis in malignant glioma, highlighting the crucial role of N-glycans in glioma and therapy resistance. This study lays the foundation for developing glycosylation-based diagnostic biomarkers and targeted therapies, potentially improving clinical outcomes for GB patients. © 2025 The Pathological Society of Great Britain and Ireland.

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来源期刊

The Journal of Pathology 医学-病理学

CiteScore

14.10

自引率

1.40%

发文量

144

审稿时长

3-8 weeks

期刊介绍： The Journal of Pathology aims to serve as a translational bridge between basic biomedical science and clinical medicine with particular emphasis on, but not restricted to, tissue based studies. The main interests of the Journal lie in publishing studies that further our understanding the pathophysiological and pathogenetic mechanisms of human disease. The Journal of Pathology welcomes investigative studies on human tissues, in vitro and in vivo experimental studies, and investigations based on animal models with a clear relevance to human disease, including transgenic systems. As well as original research papers, the Journal seeks to provide rapid publication in a variety of other formats, including editorials, review articles, commentaries and perspectives and other features, both contributed and solicited.