Novel insights into meningioma brain invasion with spatial transcriptomic profiling.

Brain invasion of meningioma is a controversial clinicopathological grading criterion that correlates with prognosis and is a stand-alone criterion for WHO grade 2 meningioma. Molecular correlates of meningioma cells and immune cell infiltration at the brain-meningioma border and its possible role in brain invasion are not known. We hypothesized that brain-invasive meningiomas have distinct gene expression profiles in meningioma cell populations and in tumour-associated microglia and macrophages (TAM) populations, most prominently at the brain-meningioma border.We performed spatial transcriptomics using NanoString GeoMx Digital Spatial Profiling to investigate the gene expression profiles of meningioma cell-enriched populations (Iba1-/CD68-) and TAM-enriched populations (Iba1+/CD68+) across 16 tumours. Regions of interest included core regions of meningiomas, the brain-meningioma border, and brain regions with confirmed invasion. Using an 1800 gene panel, we analysed differential gene expression across regions within each tumour and compared brain-invasive and non-invasive meningiomas.Meningioma cell-enriched populations from brain-invasive meningiomas (n = 8) showed significant upregulation of KRT18, implicated in filament reorganization, as well as genes involved in the cell cycle, glycolysis, and the growth factor receptor PDGFRB compared to non-invasive meningiomas (n = 8). Meningioma cell-enriched populations from the brain-meningioma border showed significant upregulation of KRT18, NDUFA4L2, and PKM relative to core areas. In TAM-enriched populations in brain tissue, we found upregulation of the chemokine receptor gene CSF1R relative to TAM-enriched populations in meningioma tissue and increased TAM infiltration in brain-invasive cases.In conclusion, our results demonstrate molecular changes in brain-invasive meningiomas compared to non-invasive meningiomas as well as spatial changes along the core-border axis. The expression pattern of TAMs also changed from meningioma to brain tissue. Additional studies are needed to confirm these findings and further reveal how we can target meningioma brain invasion.