Fiche publication
Date publication
avril 2025
Journal
NPJ precision oncology
Auteurs
Membres identifiés du Cancéropôle Est :
Dr DONTENWILL Monique
,
Pr ENTZ-WERLE Natacha
,
Dr MARTIN Sophie
,
Dr REITA Damien
Tous les auteurs :
Bernhard C, Geles K, Pawlak G, Dhifli W, Dispot A, Dusol J, Kondratova M, Martin S, Messé M, Reita D, Tulasne D, Van Seuningen I, Entz-Werle N, Ciafrè SA, Dontenwill M, Elati M
Lien Pubmed
Résumé
We present GBM-cRegMap, an online resource providing a comprehensive coregulatory influence network perspective on glioblastoma (GBM) heterogeneity and plasticity. Using representation learning algorithms, we derived two components of this resource: GBM-CoRegNet, a highly specific coregulatory network of tumor cells, and GBM-CoRegMap, a unified network influence map based on 1612 tumors from 16 studies. As a widely applicable closed-loop system connecting cellular models and tumors, GBM-cRegMap will provide the GBM research community with an easy-to-use web tool ( https://gbm.cregmap.com ) that maps any existing or newly generated transcriptomic "query" data to a reference coregulatory network and a large-scale manifold of disease heterogeneity. Using GBM-cRegMap, we demonstrated the synergy between the two components by refining the molecular classification of GBM, identifying potential key regulators, and aligning the transcriptional profiles of tumors and in vitro models. Through the amalgamation of a vast dataset, we validated the proneural (PN)-mesenchymal (MES) axis and identified three subclasses of classical (CL) tumors: astrocyte-like (CL-A), epithelial basal-like (CL-B), and cilium-rich (CL-C). We revealed the CL-C subclass, an intermediate state demonstrating the plasticity of GBM cells along the PN-MES axis under chemotherapy. We identified key regulators, such as PAX8, and NKX2.5, potentially involved in temozolomide (TMZ) resistance. Notably, NKX2.5, more expressed in higher-grade gliomas, negatively impacts patient survival, and regulates genes involved in glucose metabolism.
Référence
NPJ Precis Oncol. 2025 04 15;9(1):110