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Updated: Sep 30, 2025

Quantitative Immunohistochemistry of the Cellular Microenvironment in Patient Glioblastoma Resections
Published on: July 31, 2017
The Role of m6A Regulator-Mediated Methylation Modification and Tumor Microenvironment Infiltration in Glioblastoma
Liang Wang1, Haiyan Cao1, Ying Zhong2
1Department of Neurosurgery, Tangdu Hospital of Fourth Military Medical University, Xi'an, China.
Abstract:
N6-methyladenosine (m6A) RNA methylation is an emerging epigenetic modification in recent years and epigenetic regulation of the immune response has been demonstrated, but the potential role of m6A modification in GBM tumor microenvironment (TME) cell infiltration and stemness remain unknown. The m6A modification patterns of 310 GBM samples were comprehensively evaluated based on 21 m6A regulators, and we systematically correlated these modification patterns with TME cell infiltration characteristics and stemness characteristics. Construction of m6Ascore to quantify the m6A modification patterns of individual GBM samples using a principal component analysis algorithm. We identified two distinct patterns of m6A modification. The infiltration characteristics of TME cells in these two patterns were highly consistent with the immunophenotype of the GBM, including the immune activation differentiation pattern and the immune desert dedifferentiation pattern. We also identified two modes of regulation of immunity and stemness by m6A methylation. Stromal activation and lack of effective immune infiltration were observed in the high m6Ascore subtype. Pan-cancer analysis results illustrate a significant correlation between m6AScore and tumor clinical outcome, immune infiltration, and stemness. Our work reveals that m6A modifications play an important role in the development of TME and stemness diversity and complexity. Patients with a low m6AScore showed significant therapeutic advantages and clinical benefits. Assessing the m6A modification pattern of individual tumors will help enhance our knowledge of TME infiltration and stemness characteristics, contribute to the development of immunotherapeutic strategies.
Insights
N6-methyladenosine (m6A) RNA methylation impacts the Glioblastoma tumor microenvironment (TME). Low m6A scores correlate with better patient outcomes and therapeutic advantages, suggesting m6A patterns influence TME cell infiltration and stemness.
Area of Science:
- Epigenetics
- Cancer Biology
- Immunology
Background:
- N6-methyladenosine (m6A) RNA methylation is a key epigenetic mechanism.
- Epigenetic regulation of immune responses is established, but its role in Glioblastoma (GBM) tumor microenvironment (TME) remains unclear.
- The impact of m6A on GBM TME cell infiltration and stemness is largely unknown.
Purpose of the Study:
- To investigate the role of m6A modification patterns in GBM TME cell infiltration and stemness.
- To develop a quantitative score (m6Ascore) for m6A modification patterns in individual GBM samples.
- To correlate m6A modification patterns with TME characteristics and stemness.
Main Methods:
- Comprehensive evaluation of m6A modification patterns in 310 GBM samples using 21 m6A regulators.
- Systematic correlation analysis between m6A patterns, TME cell infiltration, and stemness characteristics.
- Construction of m6Ascore using principal component analysis.
Main Results:
- Identified two distinct m6A modification patterns associated with GBM immunophenotypes (immune activation vs. immune desert).
- Discovered two modes of m6A methylation regulating immunity and stemness, with high m6Ascore linked to stromal activation and poor immune infiltration.
- Pan-cancer analysis confirmed m6AScore's correlation with clinical outcome, immune infiltration, and stemness.
Conclusions:
- m6A modifications significantly contribute to TME complexity and stemness diversity in GBM.
- Patients with low m6Ascore exhibit improved therapeutic advantages and clinical benefits.
- Assessing m6A patterns can enhance understanding of TME infiltration and stemness, aiding immunotherapeutic strategy development.
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