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  11. Exploring The Prognostic Value Of Brms1 + Microglia Based On Single-cell Anoikis Regulator Patterns In The Immunologic Microenvironment Of Gbm

Exploring the prognostic value of BRMS1 + microglia based on single-cell anoikis regulator patterns in the immunologic microenvironment of GBM

Songyun Zhao1,2, Kaixiang Ni1,2, Jiaheng Xie3

  • 1Department of Neurosurgery, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi, China.

Journal of Neuro-Oncology
|August 14, 2024

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View abstract on PubMed

Summary
This summary is machine-generated.

Anoikis resistance in glioblastoma (GBM) is linked to a specific tumor microenvironment (TME) involving BRMS1-expressing microglia. Targeting these microglia may improve GBM prognosis and immunotherapy response.

Area of Science:

  • Oncology
  • Immunology
  • Cell Biology

Background:

  • Anoikis, a form of programmed cell death, is crucial in cancer progression.
  • Anoikis resistance is a hallmark of glioblastoma (GBM) invasion, metastasis, and therapeutic resistance.
  • The role of the anoikis-mediated tumor microenvironment (TME) in GBM pathogenesis is largely unknown.

Purpose of the Study:

  • To investigate the mechanisms of anoikis-mediated TME in glioblastoma.
  • To identify specific TME cell clusters associated with anoikis resistance and their clinical significance.
  • To explore potential therapeutic targets within the GBM TME.

Main Methods:

  • Single-cell RNA sequencing (scRNA-seq) and non-negative matrix factorization (NMF) to identify TME cell clusters.
  • TCGA and CGGA datasets for prognostic and therapeutic response analyses.
Keywords:
AnoikisGBMM2 macrophage polarizationNMF

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  • Co-culture experiments and molecular assays to validate findings and explore signaling pathways.

    • Main Results:

    • Identified CD8+ T cell and microglia clusters with distinct anoikis-associated gene signatures.
    • BRMS1-expressing microglia (BRMS1+AP-Mic) exhibited an M2 macrophage phenotype and communicated with tumor cells.
    • High BRMS1+AP-Mic expression correlated with poorer survival and immunotherapy outcomes, suggesting a role in immune suppression.

    Conclusions:

    • Anoikis-regulated TME in GBM has predictive value for prognosis and immunotherapy response.
    • BRMS1+ microglia contribute to an immunosuppressive GBM microenvironment.
    • BRMS1+ microglial cells represent a potential therapeutic target for GBM treatment.
    Tumor microenvironment
    scRNA-seq
    stRNA-seq