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A five-CpG signature of microRNA methylation in non-G-CIMP glioblastoma

Abstract : Aims: DNA methylation has been found to regulate microRNAs (miRNAs) expression, but the prognostic value of miRNA-related DNA methylation aberration remained largely elusive in cancers including glioblastomas (GBMs). This study aimed to investigate the clinical and biological feature of miRNA methylation in GBMs of non-gli-oma-CpG island methylator phenotype (non-G-CIMP). Methods: Prognostic miRNA methylation loci were analyzed, with TCGA and Rennes cohort as training sets, and independent datasets of GBMs and low-grade gliomas (LGGs) were obtained as validation sets. Different statistical and bioinformatic analysis and experimental validations were performed to clinically and biologically characterize the signature. Results: We identified and validated a risk score based on methylation status of five miRNA-associated CpGs which could predict survival of GBM patients in a series of training and validation sets. This signature was independent of age and O-6-methyl-guanine-DNA methyltransferase (MGMT) promoter methylation status. The risk subgroup was associated with angiogenesis and accordingly differential responses to bevacizumab-contained therapy. MiRNA target analysis and in vitro experiments further confirmed the accuracy of this signature. Conclusion: The five-CpG signature of miRNA methylation was biologically relevant and was of potential prognostic and predictive value for GBMs. It might be of help for improving individualized treatment. K E Y W O R D S angiogenesis, DNA methylation signature, glioblastoma, miRNA, prognostication
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En-Ming Kang, An-An Yin, Ya-Long He, Wei-Jun Chen, Amandine Etcheverry, et al.. A five-CpG signature of microRNA methylation in non-G-CIMP glioblastoma. CNS Neuroscience and Therapeutics, Wiley, 2019, 25 (9), pp.937-950. ⟨10.1111/cns.13133⟩. ⟨hal-02121050⟩

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