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A novel prognostic six-CpG signature in glioblastomas

Abstract : Aims: We aimed to identify a clinically useful biomarker using DNA methylation-based information to optimize individual treatment of patients with glioblastoma (GBM). Methods: A six-CpG panel was identified by incorporating genome-wide DNA methylation data and clinical information of three distinct discovery sets and was combined using a risk-score model. Different validation sets of GBMs and lower-grade gliomas and different statistical methods were implemented for prognostic evaluation. An integrative analysis of multidimensional TCGA data was performed to molecularly characterize different risk tumors. Results: The six-CpG risk-score signature robustly predicted overall survival (OS) in all discovery and validation cohorts and in a treatment-independent manner. It also predicted progression-free survival (PFS) in available patients. The multimarker epigenetic signature was demonstrated as an independent prognosticator and had better performance than known molecular indicators such as glioma-CpG island methylator phenotype (G-CIMP) and proneural subtype. The defined risk subgroups were molecularly distinct; high-risk tumors were biologically more aggressive with concordant activation of proangiogenic signaling at multimolecular levels. Accordingly, we observed better OS benefits of bevacizumab-contained therapy to high-risk patients in independent sets, supporting its implication in guiding usage of antiangiogenic therapy. Finally, the six-CpG signature refined the risk classification based on G-CIMP and MGMT methylation status. Conclusions: The novel six-CpG signature is a robust and independent prognostic indicator for GBMs and is of promising value to improve personalized management.
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Contributor : Xavier Chard-Hutchinson Connect in order to contact the contributor
Submitted on : Friday, April 27, 2018 - 2:06:19 PM
Last modification on : Wednesday, February 24, 2021 - 10:57:44 AM


Novel prognostic six-CpGs sign...
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An-An Yin, Nan Lu, Amandine Etcheverry, Marc Aubry, Jill Barnholtz-Sloan, et al.. A novel prognostic six-CpG signature in glioblastomas. CNS Neuroscience and Therapeutics, Wiley, 2018, 24 (3), pp.167-177. ⟨10.1111/cns.12786⟩. ⟨hal-01711026⟩



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