A novel prognostic six-CpG signature in glioblastomas
Résumé
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.
Auteurs, date et publication :
Auteurs An-An Yin , Nan Lu , Amandine Etcheverry , Marc Aubry , Jill Barnholtz‐Sloan , Lu-Hua Zhang , Jean Mosser , Wei Zhang , Xiang Zhang , Yu-He Liu , Ya-Long He
Publication : CNS Neuroscience & Therapeutics
Date : 2023
Volume : 24
Issue : 3
Pages : 167-177