Single-cell transcriptomic analysis reveals metastatic and immunosuppressive characteristics in meningioma brain-tumor interface

Abstract

Background: Meningioma is a common primary intracranial tumor with high recurrence and metastasis rate. Delineating the pathological ecosystem at the brain-tumor interface (BTI) of meningioma is critical for understanding the mechanisms of tumor metastasis and developing effective new therapies. Methods: To identify biomarkers of early metastasis and discover potential therapeutic targets, we integrated single-cell transcriptome datasets of meningioma, and identified the cell populations and molecular signatures uniquely present at the BTI. Results: A specific BTI-enriched tumor cell population with a pro-EMT (epithelial mesenchymal transition) characteristics was associated with invasion and metastasis, and ANXA2 and COL5A1 were detected as the biomarkers for these BTI-enriched tumor cells. Additionally, we characterized the BTI-specific immunosuppressive microenvironment composed of SPP1+ tumor-associated macrophages, as well as specific endothelial cells (ACKR1high) and pericytes (THY1high) promoting the highly malignant invasive state of angiogenesis. Conclusions: Collectively, BTI in meningioma is a metastatic and immunosuppressive zone. We have discovered potential biomarkers that help detect early metastasis and recurrence of meningioma.