Mapping The Evolutionary Trajectory Of Meningiomas At Single-cell Resolution

Meningiomas are nan astir communal superior encephalon tumors, accounting for astir one-third of each cardinal tense strategy (CNS) tumors. While astir are benign and manageable, 20–30% advancement to high-grade forms that behave aggressively, recur frequently, and defy modular treatments. Recurrence remains a awesome objective challenge, arsenic these tumors often return stronger, leaving patients pinch constricted therapeutic options. Despite advances successful knowing their familial and molecular profiles, really meningiomas germinate from superior to recurrent states has remained unclear.

To reside this gap, researchers from Korea University group retired to representation nan evolutionary trajectory of meningiomas astatine single-cell resolution. Their extremity was to analyse really tumor cells and their microenvironment germinate betwixt superior and recurrent disease, and to place nan molecular drivers of recurrence. Lead writer Associate Professor Jason K. Sa explains: "Our study generated nan first longitudinal single-cell atlas of matched superior and recurrent meningiomas. This assets enabled america to reconstruct tumor evolutionary trajectories and cellular hierarchies complete time, revealing profound shifts successful proliferative programs and tumor–immune interactions astatine recurrence." Their findings were published successful Nature Communications connected July 1, 2025.

The squad analyzed matched diligent samples utilizing single-nuclei RNA sequencing (snRNA-seq), which allowed profiling of some tumor cells and their surrounding microenvironment. To seizure nan move progression of tumor cells, they applied RNA velocity and latent clip analysis, search transcriptional changes arsenic tumors transitioned to recurrence. Findings were further validated utilizing outer RNA-seq datasets and immunohistochemistry (IHC), strengthening nan robustness of nan results.

The study uncovered respective cardinal insights. Recurrent meningiomas exhibited markedly higher proliferative activity compared to their superior counterparts, which were enriched successful compartment cycle–related processes. Rather than progressing linearly, recurrent tumors diverged into aggregate fierce transcriptional trajectories. Most notably, nan researchers identified COL6A3 arsenic a cardinal subordinate driving these transitions.

"We identified COL6A3 arsenic a cardinal driver of meningioma recurrence, associated pinch relapse consequence and curen resistance. Further study of tumor cell–macrophage interactions revealed that nan COL6A3–CD44 signaling cascade mediates extracellular matrix remodeling and promotes an immunosuppressive tumor microenvironment astatine recurrence," Ms. Ji Yoon Lee, nan study's first author, notes. This dual domiciled successful some tumor compartment behaviour and immune modulation makes COL6A3 an particularly compelling therapeutic target.

Dr. Sa adds, "By identifying COL6A3 arsenic a driver of malignancy successful recurrent meningiomas, we recovered its dual potential. First, arsenic a prognostic biomarker to amended stratify high-risk patients and guideline curen decisions, and second, arsenic a caller therapeutic target for supplier discovery. This opens nan doorway to precision strategies that harvester early test pinch targeted therapies to amended diligent outcomes."

This activity importantly advances our knowing of really meningiomas advancement from superior to recurrent states. It emphasizes nan request to reside some tumor compartment improvement and tumor–immune interactions erstwhile designing therapies. Looking ahead, Ms. Lee shares: "Over nan adjacent 5 to 10 years, we expect this activity tin effect diligent attraction by enabling predictive devices for radiotherapy consequence and recurrence consequence assessment."

Ultimately, targeting COL6A3 may supply a promising strategy to forestall recurrence and amended outcomes for patients pinch high-grade meningiomas.