Dataset Information

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-glioma-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-methylguanine-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.

SUBMITTER: Kang EM

PROVIDER: S-EPMC6698977 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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

Kang En-Ming EM Yin An-An AA He Ya-Long YL Chen Wei-Jun WJ Etcheverry Amandine A Aubry Marc M Barnholtz-Sloan Jill J Mosser Jean J Zhang Wei W Zhang Xiang X

CNS neuroscience & therapeutics 20190423 9

<h4>Aims</h4>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-glioma-CpG island methylator phenotype (non-G-CIMP).<h4>Methods</h4>Prognostic miRNA methylation loci were analyzed, with TCGA and Rennes cohort as training sets, and indep ...[more]

PMID: 31016891

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Project description:ObjectiveTo identify novel epigenetic signatures that could provide predictive information that is complementary to promoter methylation status of the O-6-methylguanine-DNA methyltransferase (MGMT) gene for predicting temozolomide (TMZ) response, among glioblastomas (GBMs) without glioma-CpGs island methylator phenotype (G-CIMP) METHODS: Different cohorts of primary non-G-CIMP GBMs with genome-wide DNA methylation microarray data were included for discovery and validation of a multimarker signature, combined using a RISK score model. Different statistical analyses and functional experiments were performed for clinical and biological validation.ResultsBy employing discovery cohorts with radiotherapy (RT) and TMZ versus RT alone and a strict multistep selection strategy, we identified seven CpGs, each of which was significantly correlated with overall survival (OS) of non-G-CIMP GBMs with RT/TMZ, independent of age, MGMT promoter methylation status, and other identified CpGs. A RISK score signature of the 7 CpGs was developed and validated to distinguish non-G-CIMP GBMs with differential survival outcomes to RT/TMZ, but not to RT alone. The interaction analyses also showed differential outcomes to RT/TMZ versus RT alone within the RISK score-based subgroups. The signature could also improve the risk classification by age and MGMT promoter methylation status. Functional experiments showed that HSBP2 appeared to be epigenetically regulated by one identified CpG and was associated with TMZ resistance, but it was not associated with cell proliferation or apoptosis in GBM cell lines. The predictive value of the single CpG methylation of HSBP2 by pyrosequencing was observed in a local cohort of isocitrate dehydrogenase 1 (IDH1) R132H wild-type GBMs.ConclusionsThis novel epigenetic signature might be a promising predictive (but not a general prognostic) biomarker and be helpful for refining the MGMT-based guiding approach to TMZ usage in non-G-CIMP GBMs.

Dataset Information

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

Publications

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

Similar Datasets

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