A novel methylation signature predicts extreme long-term survival in glioblastoma.

Autor: Decraene B; Department of Neurosciences, Experimental Neurosurgery and Neuroanatomy Research Group, Leuven Brain Institute (LBI), KU Leuven, Leuven, Belgium. brecht.decraene@kuleuven.be.; Department of Neurosurgery, University Hospitals Leuven, Leuven, Belgium. brecht.decraene@kuleuven.be.; Laboratory for Precision Cancer Medicine, Translational Cell and Tissue Research Unit, KU Leuven, Leuven, Belgium. brecht.decraene@kuleuven.be.; The Leuven Institute for Single-Cell Omics (LISCO), KU Leuven, Leuven, Belgium. brecht.decraene@kuleuven.be., Coppens G; Clinical Division and Laboratory of Intensive Care Medicine, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium., Spans L; Department of Human Genetics, University Hospitals Leuven, KU Leuven, Leuven, Belgium., Solie L; Department of Neurosciences, Experimental Neurosurgery and Neuroanatomy Research Group, Leuven Brain Institute (LBI), KU Leuven, Leuven, Belgium., Sciot R; Department of Pathology, University Hospitals Leuven, KU Leuven, Leuven, Belgium., Vanden Bempt I; Department of Human Genetics, University Hospitals Leuven, KU Leuven, Leuven, Belgium., De Smet F; Laboratory for Precision Cancer Medicine, Translational Cell and Tissue Research Unit, KU Leuven, Leuven, Belgium. frederik.desmet@kuleuven.be.; The Leuven Institute for Single-Cell Omics (LISCO), KU Leuven, Leuven, Belgium. frederik.desmet@kuleuven.be., De Vleeschouwer S; Department of Neurosciences, Experimental Neurosurgery and Neuroanatomy Research Group, Leuven Brain Institute (LBI), KU Leuven, Leuven, Belgium. steven.devleeschouwer@kuleuven.be.; Department of Neurosurgery, University Hospitals Leuven, Leuven, Belgium. steven.devleeschouwer@kuleuven.be.; The Leuven Institute for Single-Cell Omics (LISCO), KU Leuven, Leuven, Belgium. steven.devleeschouwer@kuleuven.be.
Jazyk: angličtina
Zdroj: Journal of neuro-oncology [J Neurooncol] 2024 Sep; Vol. 169 (2), pp. 341-347. Date of Electronic Publication: 2024 Jun 19.
DOI: 10.1007/s11060-024-04741-z
Abstrakt: Purpose: Glioblastoma (GBM) is the most common malignant primary brain tumor with a dismal prognosis of less than 2 years under maximal therapy. Despite the poor prognosis, small fractions of GBM patients seem to have a markedly longer survival than the vast majority of patients. Recently discovered intertumoral heterogeneity is thought to be responsible for this peculiarity, although the exact underlying mechanisms remain largely unknown. Here, we investigated the epigenetic contribution to survival.
Methods: GBM treatment-naïve samples from 53 patients, consisting of 12 extremely long-term survivors (eLTS) patients and 41 median-term survivors (MTS) patients, were collected for DNA methylation analysis. 865 859 CpG sites were examined and processed for detection of differentially methylated CpG positions (DMP) and regions (DMR) between both survival groups. Gene Ontology (GO) and pathway functional annotations were used to identify associated biological processes. Verification of these findings was done using The Cancer Genome Atlas (TCGA) database.
Results: We identified 67 DMPs and 5 DMRs that were associated with genes and pathways - namely reduced interferon beta signaling, in MAPK signaling and in NTRK signaling - which play a role in survival in GBM.
Conclusion: In conclusion, baseline DNA methylation differences already present in treatment-naïve GBM samples are part of genes and pathways that play a role in the survival of these tumor types and therefore may explain part of the intrinsic heterogeneity that determines prognosis in GBM patients.
(© 2024. The Author(s).)
Databáze: MEDLINE
Externí odkaz: