Transcriptomic deconvolution reveals unique tumor microenvironmental interactions across intracranial meningioma WHO grades

Abstract

Meningiomas are common tumors arising in the primary central nervous system. Although recent radiotherapy and surgical procedures have improved clinical outcomes, there remains a need for novel therapeutics to treat meningiomas resisting current approaches. To reveal putative therapeutic targets in meningioma, the present exploratory study inferred stromal and tumor compartment gene expression from bulk meningioma tumor RNA-sequencing data and revealed certain ligand-receptor interactions in tumor microenvironment which may direct future studies. Bulk tumor gene expression developed from 152 primary meningiomas encompassing WHO grades I-III were deconvolved into tumor and stromal compartment expression through non-negative linear regression using tumor purity estimates, ultimately revealing previously unknown features of tumor-stromal crosstalk in meningioma. It was found that fibroblast growth factor receptor 4 (FGFR4) and human epidermal growth factor receptor 4 (HER4) was implicated in multiple tumor-stroma interactions. Specific chemokine receptors, such as CCR4 and CCR7, were frequently involved in stroma-stroma crosstalk. Additionally, genes reflecting immune-exhausted T cell responses also displayed distinct expression across the WHO grades. Taken together, the findings reveal potential therapeutic targets which should be investigated further.