Mpscore: A Novel Predictive And Prognostic Scoring For Progressive Meningioma

Simple SummarySubtyping for meningioma is urgently required to stratify the patients with high risks of recurrence and progression due to the intertumoral heterogeneity in meningioma. Here, we performed a consensus clustering of 179 meningiomas and identified progressive subtype (subtype 3) based the transcriptome profiles. Loss of chromosome 1q along with Neurofibromin 2 (NF2) mutation or loss of chromosome 22p is exclusively presented in subtype 3 meningioma. DNA methylation analyses of meningioma subtypes also suggested hypermethylation was observed in subtype 3 meningioma. Our findings identified low expression of Alkaline Phosphatase (ALPL) is the most significant feature in progressive subtype of meningioma. We constructed and validated a meningioma progression score (MPscore) to characterize the progressive phenotype in meningioma. The predictive accuracy has also been validated in three independent cohorts. Therefore, MPscore can be potentially useful for meningioma recurrence prediction and stratification.Meningioma is the most common tumor in central nervous system (CNS). Although most cases of meningioma are benign (WHO grade I) and curable by surgical resection, a few tumors remain diagnostically and therapeutically challenging due to the frequent recurrence and progression. The heterogeneity of meningioma revealed by DNA methylation profiling suggests the demand of subtyping for meningioma. Therefore, we performed a clustering analyses to characterize the progressive features of meningioma and constructed a meningioma progression score to predict the risk of the recurrence. A total of 179 meningioma transcriptome from RNA sequencing was included for progression subtype clustering. Four biologically distinct subtypes (subtype 1, subtype 2, subtype 3 and subtype 4) were identified. Copy number alternation and genomewide DNA methylation of each subtype was also characterized. Immune cell infiltration was examined by the microenvironment cell populations counter. All anaplastic meningiomas (7/7) and most atypical meningiomas (24/32) are enriched in subtype 3 while no WHO II or III meningioma presents in subtype 1, suggesting subtype 3 meningioma is a progressive subtype. Stemness index and immune response are also heterogeneous across four subtypes. Monocytic lineage is the most immune cell type in all meningiomas, except for subtype 1. CD8 positive T cells are predominantly observed in subtype 3. To extend the clinical utility of progressive meningioma subtyping, we constructed the meningioma progression score (MPscore) by the signature genes in subtype 3. The predictive accuracy and prognostic capacity of MPscore has also been validated in three independent cohort. Our study uncovers four biologically distinct subtypes in meningioma and the MPscore is potentially helpful in the recurrence risk prediction and response to treatments stratification in meningioma.