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.PGK1was 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.
背景：脑膜瘤是成人常见的颅内肿瘤。大多数为良性WHO I级（GI）肿瘤，约20%被诊断为更具侵袭性的WHO II级（GII）和III级（GIII）脑膜瘤。本研究旨在识别与肿瘤分级相关的表达基因，并评估其功能相关性。 方法：采用RNA测序（RNA-seq）技术分析良性脑膜上皮型（n=19）与纤维型（n=11）、非典型性（n=18）及间变性（n=12）脑膜瘤的转录组。对数据进行差异基因表达分析和基因集富集分析（GSEA）。利用已公开的单细胞RNA测序数据集定义脑膜瘤细胞组成及细胞类型特异性基因表达，实现对RNA-seq数据的反卷积分析。 结果：无监督分析显示三个肿瘤聚类，分别对应脑膜上皮型（GI）、纤维型（GI）及非典型性/间变性（GII/GIII）脑膜瘤的组织学亚型。差异分析鉴定出5518个具有分级相关表达变化的蛋白质编码基因。GSEA分析表明高级别脑膜瘤富集于细胞增殖、核糖体生物合成及代谢过程，而良性肿瘤则富集于细胞形态发生、跨膜离子转运和免疫调节过程。PGK1是最显著的分级相关基因，免疫组化证实磷酸甘油酸激酶1在GII和GIII肿瘤中的表达增加。RNA-seq数据反卷积分析揭示了肿瘤微环境的分级相关变化，特别是从WHO GI级到GIII级肿瘤中边界相关巨噬细胞的进行性减少。 结论：本研究系统阐明了高级别脑膜瘤中失调的关键基因与生物学过程，包括代谢重编程、离子转运紊乱、免疫调节改变等尚未充分认知的机制，以及良性与侵袭性肿瘤间肿瘤微环境的差异。
Determining the Biological Features of Aggressive Meningioma Growth with Transcriptomic Profiling
肿瘤(癌症)患者之家