Novel insights into meningioma brain invasion with spatial transcriptomic profiling

Area of Science:

• Neuro-oncology
• Molecular pathology
• Genomics

Background:

• Brain invasion is a key factor in meningioma grading and prognosis.
• The molecular mechanisms underlying meningioma brain invasion remain largely unknown.
• Understanding these mechanisms is crucial for developing targeted therapies.

Purpose of the Study:

• To investigate the distinct gene expression profiles of meningioma cells and tumor-associated microglia and macrophages (TAMs) in brain-invasive versus non-invasive meningiomas.
• To explore spatial gene expression changes at the brain-meningioma border.
• To identify molecular correlates of meningioma brain invasion.

Main Methods:

• Spatial transcriptomics using NanoString GeoMx Digital Spatial Profiling on 16 meningioma tumors.
• Analysis of meningioma cell-enriched (Iba1-/CD68-) and TAM-enriched (Iba1+/CD68+) populations.
• Differential gene expression analysis across tumor core, brain-meningioma border, and invaded brain regions.

Main Results:

• Brain-invasive meningiomas exhibited upregulation of KRT18, cell cycle, glycolysis, and PDGFRB genes in meningioma cells.
• Spatial analysis revealed increased KRT18, NDUFA4L2, and PKM expression at the brain-meningioma border.
• TAMs showed altered CSF1R expression and increased infiltration in brain-invasive cases.

Conclusions:

• Brain invasion in meningiomas is associated with specific molecular alterations in both tumor and immune cells.
• Distinct gene expression patterns exist along the tumor core-to-brain invasion axis.
• Further research is needed to validate these findings and explore therapeutic targeting of meningioma brain invasion.