Brecht Decraene, Grégoire Coppens, Lien Spans, Lien Solie, Raf Sciot, Isabelle Vanden Bempt, Frederik De Smet, Steven De Vleeschouwer
{"title":"一种新型甲基化特征可预测胶质母细胞瘤的极端长期生存率。","authors":"Brecht Decraene, Grégoire Coppens, Lien Spans, Lien Solie, Raf Sciot, Isabelle Vanden Bempt, Frederik De Smet, Steven De Vleeschouwer","doi":"10.1007/s11060-024-04741-z","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":16425,"journal":{"name":"Journal of Neuro-Oncology","volume":null,"pages":null},"PeriodicalIF":3.2000,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11341684/pdf/","citationCount":"0","resultStr":"{\"title\":\"A novel methylation signature predicts extreme long-term survival in glioblastoma.\",\"authors\":\"Brecht Decraene, Grégoire Coppens, Lien Spans, Lien Solie, Raf Sciot, Isabelle Vanden Bempt, Frederik De Smet, Steven De Vleeschouwer\",\"doi\":\"10.1007/s11060-024-04741-z\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>\",\"PeriodicalId\":16425,\"journal\":{\"name\":\"Journal of Neuro-Oncology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.2000,\"publicationDate\":\"2024-09-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11341684/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Neuro-Oncology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s11060-024-04741-z\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/6/19 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q2\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Neuro-Oncology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s11060-024-04741-z","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/6/19 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
A novel methylation signature predicts extreme long-term survival in glioblastoma.
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.
期刊介绍:
The Journal of Neuro-Oncology is a multi-disciplinary journal encompassing basic, applied, and clinical investigations in all research areas as they relate to cancer and the central nervous system. It provides a single forum for communication among neurologists, neurosurgeons, radiotherapists, medical oncologists, neuropathologists, neurodiagnosticians, and laboratory-based oncologists conducting relevant research. The Journal of Neuro-Oncology does not seek to isolate the field, but rather to focus the efforts of many disciplines in one publication through a format which pulls together these diverse interests. More than any other field of oncology, cancer of the central nervous system requires multi-disciplinary approaches. To alleviate having to scan dozens of journals of cell biology, pathology, laboratory and clinical endeavours, JNO is a periodical in which current, high-quality, relevant research in all aspects of neuro-oncology may be found.