Single-cell RNA sequencing reveals cellular senescence functions as a prognostic and therapeutic indicator in meningiomas

Abstract

Abstract Meningiomas rank among the most prevalent solid tumors in the human central nervous system, exhibiting a wide spectrum of prognoses, with particularly challenging outcomes in cases of malignant meningiomas. Cellular senescence (CS) is recognized as a significant prognostic and therapeutic indicator in numerous types of tumors. However, the characterization of CS in meningiomas has remained largely unexplored. This study delves into cellular senescence (CS) as a prognostic and therapeutic factor in meningiomas, a relatively unexplored area. Using CellAge database genes, we established a CS score index. Survival analysis, employing R packages like "survival" and "survminer," identified genes with significant Recurrence-Free Survival (RFS) differences. Weighted Gene Co-expression Network Analysis (WGCNA) and Multi-scale Embedded Gene Co-expression Network Analysis (MEGENA) revealed hub genes. The Tumor Immune Dysfunction and Exclusion (TIDE) score assessed immunotherapy potential, while the RNAactDrug database predicted drug sensitivity. Our analysis unveiled a strong link between CS score, meningioma recurrence, and grade. Notably, we observed differential senescence-associated secretory phenotype (SASP) expression in recurrent versus non-recurrent meningiomas. Single cell sequencing exposed distinct senescence subgroups and heterogeneity within meningioma. We also elucidated mechanisms through which CS negatively affects prognosis. TBL3, an identified hub gene, emerged as a promising prognostic factor and therapeutic target. Our study pinpointed Panobinostat and Palbociclib as potential TBL3 and CS inhibitors, potentially broadening therapeutic options, especially for malignant meningiomas. In summary, this research underscores the potential of CS as both a prognostic indicator and a target for therapeutic interventions in the context of meningiomas.