Dataset Information
Human Mitochondrial Ribosomal RNA Modification-Based Classification Contributes to Discriminate the Prognosis and Immunotherapy Response of Glioma Patients.
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ABSTRACT: Background
Epigenetic regulations of the tumor microenvironment (TME) and immunotherapy have been investigated in recent years. Nevertheless, the potential value of mitochondrial ribosomal RNA (mt-rRNA) modification in regulation of the TME and immunotherapy remains unknown.Methods
We comprehensively investigated the mt-rRNA-modification patterns in glioma patients based on nine regulators of mt-rRNA. Subsequently, these modification patterns were correlated systematically with immunologic characteristics and immunotherapy. An "mt-rRNA predictor" was constructed and validated in multiple publicly available cohorts to provide guidance for prognosis prediction and immunotherapy of glioma patients.Results
Two distinct patterns of mt-rRNA modification were determined based on the evidence that nine regulators of mt-rRNA correlated significantly with most clinicopathologic characteristics, immunomodulators, TME, immune-checkpoint blockers (ICBs), and prognosis. Patients with mt-rRNA subtype II presented significantly poorer overall survival/progression-free survival (OS/PFS), but higher tumor mutational burden (TMB), more somatic mutations, and copy number variation (CNV). These two mt-rRNA subtypes had distinct TME patterns and responses to ICB therapy. An mt-rRNA predictor was constructed and validated in four glioma cohorts. The subtype with high mt-rRNA score, characterized by increased TMB, infiltration of immune cells, and activation of immunity, suggested an immune-activated phenotype, and was also linked to greater sensitivity to immunotherapy using anti-programmed cell death protein 1 (PD-1) but resistance to temozolomide.Conclusions
Regulators of mt-rRNA modification have indispensable roles in the complexity and diversity of the TME and prognosis. This novel classification based on patterns of mt-rRNA modification could provide an effective prognostic predictor and guide more appropriate immunotherapy/chemotherapy strategies for glioma patients.
SUBMITTER: Wang P
PROVIDER: S-EPMC8458820 | biostudies-literature | 2021
REPOSITORIES: biostudies-literature
Publications
Human Mitochondrial Ribosomal RNA Modification-Based Classification Contributes to Discriminate the Prognosis and Immunotherapy Response of Glioma Patients.
Frontiers in immunology 20210909
<h4>Background</h4>Epigenetic regulations of the tumor microenvironment (TME) and immunotherapy have been investigated in recent years. Nevertheless, the potential value of mitochondrial ribosomal RNA (mt-rRNA) modification in regulation of the TME and immunotherapy remains unknown.<h4>Methods</h4>We comprehensively investigated the mt-rRNA-modification patterns in glioma patients based on nine regulators of mt-rRNA. Subsequently, these modification patterns were correlated systematically with i ...[more]