Abstract
Glioblastoma multiforme (GBM) is the most aggressive type of primary brain tumor, and the presence of glioma stem cells (GSCs) has been linked to its resistance to treatments and recurrence. Additionally, aberrant glycosylation has been implicated in the aggressiveness of cancers. However, the influence and underlying mechanism of N-glycosylation on the GSC phenotype and GBM malignancy remain elusive. Here, we performed an in-silico analysis approach on publicly available datasets to examine the function of N-glycosylation-related genes in GSCs and gliomas, accompanied by a qRT-PCR validation experiment. We found that high α-1,2-mannosidase MAN1C1 is associated with immunological functions and worse survival of glioma patients. Differential gene expression analysis and qRT-PCR validation revealed that MAN1C1 is highly expressed in GSCs. Furthermore, higher MAN1C1 expression predicts worse outcomes in glioma patients. Also, MAN1C1 expression is increased in the perinecrotic region of GBM and is associated with immunological and inflammatory functions, a hallmark of the GBM mesenchymal subtype. Further analysis confirmed that MAN1C1 expression is closely associated with infiltrating immune cells and disrupted immune response in the GBM microenvironment. These suggest that MAN1C1 is a potential biomarker for gliomas and may be important as an immunotherapeutic target for GBM.
Overview
- The study investigates the influence of N-glycosylation on the GSC phenotype and GBM malignancy using an in-silico analysis approach and qRT-PCR validation experiment. The hypothesis being tested is that N-glycosylation-related genes play a role in the aggressiveness of GBM and GSCs. The methodology used for the experiment includes publicly available datasets for gene expression analysis and qRT-PCR validation. The primary objective of the study is to identify potential biomarkers and immunotherapeutic targets for GBM and GSCs based on N-glycosylation-related genes.
Comparative Analysis & Findings
- The study found that high α-1,2-mannosidase MAN1C1 is associated with immunological functions and worse survival of glioma patients. Differential gene expression analysis and qRT-PCR validation revealed that MAN1C1 is highly expressed in GSCs and predicts worse outcomes in glioma patients. Additionally, MAN1C1 expression is increased in the perinecrotic region of GBM and is associated with immunological and inflammatory functions, a hallmark of the GBM mesenchymal subtype. Further analysis confirmed that MAN1C1 expression is closely associated with infiltrating immune cells and disrupted immune response in the GBM microenvironment. These findings suggest that MAN1C1 is a potential biomarker for gliomas and may be important as an immunotherapeutic target for GBM.
Implications and Future Directions
- The study's findings highlight the importance of N-glycosylation-related genes in the aggressiveness of GBM and GSCs. The identification of MAN1C1 as a potential biomarker and immunotherapeutic target for GBM and GSCs could lead to the development of new immunotherapies for these aggressive brain tumors. However, the study has limitations, such as the use of publicly available datasets, which may not be representative of all GBM and GSCs. Future research should validate the findings using in vivo models and clinical samples to confirm the role of N-glycosylation-related genes in GBM and GSCs. Additionally, further studies should investigate the mechanisms underlying the association between MAN1C1 and the immune response in the GBM microenvironment.