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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MDPI AG
2024-12-01
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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. |
format | Article |
id | doaj-art-fafae91ad37b4f3ba642b4ec10a0b498 |
institution | Kabale University |
issn | 2813-3757 |
language | English |
publishDate | 2024-12-01 |
publisher | MDPI AG |
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series | Kinases and Phosphatases |
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 |