COSMC-Regulated O-Glycosylation: A Bioinformatics-Driven Biomarker Identification for Stratifying Glioblastoma Stem Cell Subtypes

Glioblastoma stem cells (GSCs) are key drivers of relapse, metastasis, and therapy resistance in glioblastoma due to their adaptability and diversity, which make them challenging to target effectively. This study explores the O-glycosylation in differentiating two key GSC subtypes, CD133 and CD44. W...

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Main Authors: Sara Sadat Aghamiri, Rada Amin
Format: Article
Language:English
Published: MDPI AG 2024-12-01
Series:Kinases and Phosphatases
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Online Access:https://www.mdpi.com/2813-3757/2/4/25
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author Sara Sadat Aghamiri
Rada Amin
author_facet Sara Sadat Aghamiri
Rada Amin
author_sort Sara Sadat Aghamiri
collection DOAJ
description Glioblastoma stem cells (GSCs) are key drivers of relapse, metastasis, and therapy resistance in glioblastoma due to their adaptability and diversity, which make them challenging to target effectively. This study explores the O-glycosylation in differentiating two key GSC subtypes, CD133 and CD44. We utilized the TCGA dataset of GBM and presented the reproducible bioinformatics analysis for our results. Our profiling showed enriched O-glycosylation signatures in CD44-expressing GBM cells over CD133, with Cosmc, the chaperone for core mucin-type O-glycosylation, significantly upregulated in the CD44-positive group. Moreover, Cosmc was associated with shorter progression-free intervals, suggesting its potential as an indicator of aggressive disease. High Cosmc expression also enriched immune-related pathways, including inflammatory response and antigen presentation, and was associated with presence of myeloid cells, T cells, and NK cells. Additionally, elevated Cosmc correlated with extracellular matrix (ECM) pathways and stromal cell populations, such as perivascular fibroblasts. These findings position O-glycosylation, specially, Cosmc as a promising biomarker for distinguishing GSC subclones, with relevance to immune modulation, and ECM dynamics, identifying it as a potential target for novel GBM therapies.
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spelling doaj-art-fafae91ad37b4f3ba642b4ec10a0b4982025-01-24T13:37:30ZengMDPI AGKinases and Phosphatases2813-37572024-12-012439141210.3390/kinasesphosphatases2040025COSMC-Regulated O-Glycosylation: A Bioinformatics-Driven Biomarker Identification for Stratifying Glioblastoma Stem Cell SubtypesSara Sadat Aghamiri0Rada Amin1Department of Biochemistry, University of Nebraska, Lincoln, NE 68503, USADepartment of Biochemistry, University of Nebraska, Lincoln, NE 68503, USAGlioblastoma stem cells (GSCs) are key drivers of relapse, metastasis, and therapy resistance in glioblastoma due to their adaptability and diversity, which make them challenging to target effectively. This study explores the O-glycosylation in differentiating two key GSC subtypes, CD133 and CD44. We utilized the TCGA dataset of GBM and presented the reproducible bioinformatics analysis for our results. Our profiling showed enriched O-glycosylation signatures in CD44-expressing GBM cells over CD133, with Cosmc, the chaperone for core mucin-type O-glycosylation, significantly upregulated in the CD44-positive group. Moreover, Cosmc was associated with shorter progression-free intervals, suggesting its potential as an indicator of aggressive disease. High Cosmc expression also enriched immune-related pathways, including inflammatory response and antigen presentation, and was associated with presence of myeloid cells, T cells, and NK cells. Additionally, elevated Cosmc correlated with extracellular matrix (ECM) pathways and stromal cell populations, such as perivascular fibroblasts. These findings position O-glycosylation, specially, Cosmc as a promising biomarker for distinguishing GSC subclones, with relevance to immune modulation, and ECM dynamics, identifying it as a potential target for novel GBM therapies.https://www.mdpi.com/2813-3757/2/4/25cancer stem cellsglioblastomaO-glycosylationCosmcCD44CD133
spellingShingle Sara Sadat Aghamiri
Rada Amin
COSMC-Regulated O-Glycosylation: A Bioinformatics-Driven Biomarker Identification for Stratifying Glioblastoma Stem Cell Subtypes
Kinases and Phosphatases
cancer stem cells
glioblastoma
O-glycosylation
Cosmc
CD44
CD133
title COSMC-Regulated O-Glycosylation: A Bioinformatics-Driven Biomarker Identification for Stratifying Glioblastoma Stem Cell Subtypes
title_full COSMC-Regulated O-Glycosylation: A Bioinformatics-Driven Biomarker Identification for Stratifying Glioblastoma Stem Cell Subtypes
title_fullStr COSMC-Regulated O-Glycosylation: A Bioinformatics-Driven Biomarker Identification for Stratifying Glioblastoma Stem Cell Subtypes
title_full_unstemmed COSMC-Regulated O-Glycosylation: A Bioinformatics-Driven Biomarker Identification for Stratifying Glioblastoma Stem Cell Subtypes
title_short COSMC-Regulated O-Glycosylation: A Bioinformatics-Driven Biomarker Identification for Stratifying Glioblastoma Stem Cell Subtypes
title_sort cosmc regulated o glycosylation a bioinformatics driven biomarker identification for stratifying glioblastoma stem cell subtypes
topic cancer stem cells
glioblastoma
O-glycosylation
Cosmc
CD44
CD133
url https://www.mdpi.com/2813-3757/2/4/25
work_keys_str_mv AT sarasadataghamiri cosmcregulatedoglycosylationabioinformaticsdrivenbiomarkeridentificationforstratifyingglioblastomastemcellsubtypes
AT radaamin cosmcregulatedoglycosylationabioinformaticsdrivenbiomarkeridentificationforstratifyingglioblastomastemcellsubtypes