The Non-N6-Methyladenosine Epitranscriptome Patterns and Characteristics of Tumor Microenvironment Infiltration and Mesenchymal Transition in Glioblastoma.

Jianye Xu,Shaobo Wang,Hao Xue,Yang Fan,Zijie Gao,Ping Zhang,Gang Li,Qingtong Wang,Lin Deng,Zongpu Zhang,Kaining Liu,Huizhi Wang,Rongrong Zhao,Xing Guo

doi:10.3389/fimmu.2021.809808

Abstract

BackgroundAn increasing number of RNA modification types other than N6-methyladenosine (m6A) modification have been detected. Nonetheless, the probable functions of RNA modifications beyond m6A in the tumor microenvironment (TME), mesenchymal (MES) transition, immunotherapy, and drug sensitivity remain unclear.MethodsWe analyzed the characteristics of 32 non-m6A RNA modification regulators in 539 glioblastoma (GBM) patients and the TME cell infiltration and MES transition patterns. Using principal component analysis, a non-m6A epitranscriptome regulator score (RM score) model was established. We estimated the association between RM score and clinical characteristics, TME status, GBM subtypes, and drug and immunotherapy response.ResultsThree definite non-m6A RNA modification patterns associated with diverse biological pathways and clinical characteristics were identified. The high RM score group was characterized by a poor prognosis, enhanced immune infiltration, and MES subtype. Further analysis indicated that the high RM score group had a lower tumor mutation burden as well as a weaker response to immunotherapy. The higher RM score group may benefit more from drugs targeting the EGFR and WNT signaling pathways.ConclusionOur study exposed the potential relationship of non-m6A RNA modification regulators with clinical features, TME status, and GBM subtype and clarified its therapeutic value.

Highlights

Glioblastoma (GBM) is the most ordinary malignant intracranial cancer [1]
The investigation of 32 non-modification types other than N6methyladenosine (m6A) RNA modification regulators exhibited that CNV-related mutations were widespread
To determine whether genetic variations affected nonm6A RNA modification regulator expression among GBM cases, we analyzed the expression of these regulators between GBM and normal samples to determine whether CNV alterations could result in perturbations in non-m6A RNA modification regulator expression

Summary

Introduction

Glioblastoma (GBM) is the most ordinary malignant intracranial cancer [1]. Patients with GBM have an approximately 14–16-month median survival time, and GBM is highly resistant to standard therapies because of its extraordinary immunosuppressive microenvironment and mesenchymal (MES) transition [2,3,4].There are over 160 posttranscriptional RNA modifications [5]. The probable functions of RNA modifications beyond m6A in the tumor microenvironment (TME), mesenchymal (MES) transition, immunotherapy, and drug sensitivity remain unclear. Methods: We analyzed the characteristics of 32 non-m6A RNA modification regulators in 539 glioblastoma (GBM) patients and the TME cell infiltration and MES transition patterns. We estimated the association between RM score and clinical characteristics, TME status, GBM subtypes, and drug and immunotherapy response. Results: Three definite non-m6A RNA modification patterns associated with diverse biological pathways and clinical characteristics were identified. Further analysis indicated that the high RM score group had a lower tumor mutation burden as well as a weaker response to immunotherapy. Conclusion: Our study exposed the potential relationship of non-m6A RNA modification regulators with clinical features, TME status, and GBM subtype and clarified its therapeutic value

Methods

Results

Discussion

Conclusion