A prognostic matrix code defines functional glioblastoma phenotypes and niches.

Area of Science:

• Oncology
• Molecular Biology
• Immunology

Background:

• Glioblastoma (GBM) malignancy and treatment response are influenced by tumor, immune, and vascular niches.
• The role of extracellular matrix proteins (CMPs) in mediating these interactions is not fully understood.

Purpose of the Study:

• To characterize the functional and clinical relevance of CMP-encoding genes in GBM.
• To identify a "matrix code" for GBM stratification and therapeutic targeting.

Main Methods:

• Analysis of GBM at bulk, single-cell, and spatial resolutions.
• Gene expression profiling of CMPs.
• Correlation analysis with clinical outcomes, oncogenic alterations, immune infiltration, and anatomical structures.

Main Results:

• A "matrix code" was identified, categorizing GBM into matrisome-high (worse survival) and matrisome-low (better survival) groups.
• Matrisome enrichment is linked to mesenchymal state, pro-tumor immune cells, and immune checkpoint genes.
• Matrisome genes are enriched in vascular and infiltrative regions harboring glioma stem cells.
• A 17-gene matrisome signature refines prognostic value and may predict response to PD1 blockade.

Conclusions:

• Matrisome gene expression profiles serve as biomarkers for GBM niches, immune crosstalk, and patient stratification.
• This signature can optimize treatment strategies and predict response to immunotherapy in GBM.