MPscore: A Novel Predictive and Prognostic Scoring for Progressive Meningioma

Abstract

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.

Integrated Molecular Analysis Reveals 2 Distinct Subtypes of Pure Seminoma of the Testis

“…Recent progress in understanding the molecular heterogeneity of cancer types and intertumoral heterogeneity has suggested improvements for therapeutic strategies. 29 , 30 A large variety of cancer types such as meningioma, 31 pancreatic neuroendocrine tumors, 32 and squamous cell carcinoma of the head and neck 33 reveal the existence of clinically relevant subtypes with distinctive molecular characteristics. Moreover, clinically relevant subtypes for breast 34 , 35 and lung cancer 36 have led to different treatment strategies in the clinic, which highlights the importance of subtype-specific therapy.…”

The integrated multiomic diagnosis of sporadic meningiomas: a review of its clinical implications

“…Prediction of tumor behavior through genomic mutation analysis is beginning to guide clinical decisions. Increasingly, predictive scores are being developed based on integrated transcriptome data [ 56 ], and grading systems are being proposed based on epigenomic modifications and chromosomal variations [ 33 , 57 ]. One DNA methylation-based classification identified low grade, “benign” tumors, with high, rapid recurrence risk, and conversely, higher grade tumors with lower risk.…”

m6A Methylation Regulators Are Predictive Biomarkers for Tumour Metastasis in Prostate Cancer

“…Compared to the overall survival of all PCas, prediction of metastasis would be more helpful in the clinical practice, as most primary PCa is localized. Therefore, through applying consensus clustering of gene expression, we can predict the cancer metastasis more accurately than through conventional histopathology [ 51 ]. Combined with other parameters such as clinical information and MRI, our score could help establish a strategy for PCa to inform clinicians on whether to escalate or deescalate the current treatment, though it requires validation in a multi-center prospective clinical trial [ 8 , 10 ].…”