m6A Regulator Expression Segregates Meningiomas Into Biologically Distinct Subtypes

Jiawei Chen; Shuchen Sun; Leihao Ren; Lingyang Hua; Daijun Wang; Qing Xie; Hans-Georg Wirsching; Jiaojiao Deng; Michael Weller; Ye Gong

doi:10.3389/fonc.2021.760892

m⁶A Regulator Expression Segregates Meningiomas Into Biologically Distinct Subtypes

Front Oncol. 2021 Dec 22:11:760892. doi: 10.3389/fonc.2021.760892. eCollection 2021.

Authors

Jiawei Chen^{1

2

3}, Shuchen Sun^{1

2

3}, Leihao Ren^{1

2

3}, Lingyang Hua^{1

2

3}, Daijun Wang^{1

2

3}, Qing Xie^{1

2

3}, Hans-Georg Wirsching⁴, Jiaojiao Deng^{1

2

3}, Michael Weller⁴, Ye Gong^{1

2

3

5}

Affiliations

¹ Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China.
² Institute of Neurosurgery, Fudan University, Shanghai, China.
³ Shanghai Key Laboratory of Brain Function Restoration and Neural Regeneration, Fudan University, Shanghai, China.
⁴ Department of Neurology, University Hospital and University of Zurich, Zurich, Switzerland.
⁵ Department of Critical Care Medicine, Huashan Hospital, Fudan University, Shanghai, China.

Abstract

Background: Meningiomas are the most common primary intracranial tumors in adults. According to the 2021 World Health Organization (WHO) classification of central nervous system tumors, approximately 80% of meningiomas are WHO grade 1, that is, histopathologically benign, whereas about 20% are WHO grade 2 or grade 3, showing signs of atypia or malignancy. The dysregulation of N6-methylation (m⁶A) regulators is associated with disorders of diverse critical biological processes in human cancer. This study aimed to explore whether m⁶A regulator expression was associated with meningioma molecular subtypes and immune infiltration.

Methods: We evaluated the m⁶A modification patterns of 160 meningioma samples based on 19 m⁶A regulators and correlated them with immune infiltration characteristics. Novel molecular subtypes were defined based on prognostic hub gene expression.

Results: Two meningioma clusters were identified based on the expression of 19 m⁶A regulators. In cluster 1, 607 differentially expressed genes (DEGs) were upregulated and 519 were downregulated. A total of 1,126 DEGs comprised three gene expression modules characterized by turquoise, blue, and gray. Functional annotation suggested that the turquoise module was involved in Wnt-related and other important cancer-related pathways. We identified 32 hub genes in this module by constructing a protein-protein interaction network. The meningioma samples were divided into two molecular subtypes. EPN1, EXOSC4, H2AX, and MZT2B not only showed significant differences between meningioma molecular subtypes but also had the potential to be the marker genes of specific meningioma subtypes.

Conclusion: m⁶A regulator gene expression may be a novel prognostic marker in meningioma.

Keywords: WGCNA; immune infiltration; m6A; meningioma; molecular subtype.