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Background  An increasing number of RNA modification types other than N 6 -methyladenosine (m 6 A) modification have been detected. Nonetheless, the probable functions of RNA modifications beyond m 6 A in the tumor microenvironment (TME), mesenchymal (MES) transition, immunotherapy, and drug sensitivity remain unclear.    Methods  We analyzed the characteristics of 32 non-m 6 A RNA modification regulators in 539 glioblastoma (GBM) patients and the TME cell infiltration and MES transition patterns. Using principal component analysis, a non-m 6 A 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-m 6 A 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-m 6 A RNA modification regulators with clinical features, TME status, and GBM subtype and clarified its therapeutic value.

frontiers in immunology

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