Background: Meningiomas are common intracranial tumors in adults. Most are benign WHO grade I (GI) tumors, while approximately 20% are diagnosed as more aggressive WHO grade II (GII) and grade III (GIII) meningiomas. The study aimed to identify genes with tumor grade-related expression and to assess their functional relevance. Methods: RNA sequencing (RNA-seq) was performed to analyze transcriptomes of benign meningothelial (n = 19) and fibrous (n = 11), atypical (n = 18) and anaplastic (n = 12) meningiomas. The data were analyzed for differential genes expression and Gene Set Enrichment Analysis (GSEA). A deposited scRNA-seq dataset was used to define meningioma cellular composition and cell type-specific gene expression enabling deconvolution of RNA-seq data. Results: Unsupervised analysis revealed three tumor clusters corresponding to the histological subtypes of meningothelial (GI), fibrous (GI) and atypical/anaplastic (GII/GIII) meningiomas. Differential analysis identified 5518 protein-coding genes with grade-related changes in expression. GSEA showed that high-grade meningiomas were enriched for processes of cell proliferation, ribosome biogenesis, and metabolism, whereas benign tumors were enriched for cell morphogenesis, transmembrane ion transport, and immune regulation. PGK1 was the most significantly grade-related gene and increased expression of phosphoglycerate kinase 1 in GII and GIII tumors was confirmed by immunohistochemistry. Deconvolution of RNA-seq data revealed grade-related changes in the tumor microenvironment, notably a progressive decrease in border-associated macrophages from WHO GI to GIII tumors. Conclusions: In our study, we characterized key genes and processes dysregulated in high-grade meningiomas, including less understood mechanisms such as metabolic reprogramming, disrupted ion transport, altered immune regulation, and differences in the tumor microenvironment between benign and aggressive tumors.
Baluszek et al. (Wed,) studied this question.