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

Abstract

Background: An 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.

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. 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.

Results: Three 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.

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.

Keywords: glioblastoma; immunotherapy; mesenchymal transition; non-m6A RNA modification; tumor microenvironment.