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Unger, K. ; Fleischmann, D.F.* ; Ruf, V.* ; Felsberg, J.* ; Piehlmaier, D. ; Samaga, D. ; Hess J. ; Suresh, M.P.* ; Mittelbronn, M.* ; Lauber, K. ; Budach, W.* ; Säbel, M.* ; Rödel, C.* ; Reifenberger, G.* ; Herms, J.* ; Tonn, J.C.* ; Zitzelsberger, H. ; Belka, C. ; Niyazi, M.*

Improved risk stratification in younger IDH wild-type glioblastoma patients by combining a 4-miRNA signature with MGMT promoter methylation status.

Neurooncol. Adv. 2:vdaa137 (2020)
Verlagsversion Forschungsdaten DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Background: The potential benefit of risk stratification using a 4-miRNA signature in combination with MGMT promoter methylation in IDH1/2 wild-type glioblastoma patients was assessed. Methods: Primary tumors from 102 patients with comparable treatment from the LMU Munich (n = 37), the University Hospital Düsseldorf (n = 33), and The Cancer Genome Atlas (n = 32) were included. Risk groups were built using expressions of hsa-let-7a-5p, hsa-let-7b-5p, hsa-miR-615-5p, and hsa-miR-125a-5p to assess prognostic performance in overall survival (OS). MGMT promoter methylation and age were considered as cofactors. Integrated miRNA, DNA methylome, and transcriptome analysis were used to explore the functional impact of signature miRNAs. Results: The 4-miRNA signature defined high-risk (n = 46, median OS: 15.8 months) and low-risk patients (n = 56, median OS: 20.7 months; univariable Cox proportional hazard analysis: hazard ratio [HR]: 1.8, 95% confidence interval [CI]: 1.14-2.83, P = .01). The multivariable Cox proportional hazard model including the 4-miRNA signature (P = .161), MGMT promoter methylation (P < .001), and age (P = .034) significantly predicted OS (Log-rank P < .0001). Likewise to clinical routine, analysis was performed for younger (≤60 years, n = 50, median OS: 20.2 months) and older patients (>60 years, n = 52, median OS: 15.8) separately. In younger patients, the 4-miRNA signature had prognostic value (HR: 1.92, 95% CI: 0.93-3.93, P = .076). Particularly, younger, MGMT methylated, 4-miRNA signature low-risk patients (n = 18, median OS: 37.4 months) showed significantly improved survival, compared to other younger patients (n = 32, OS 18.5 months; HR: 0.33, 95% CI: 0.15-0.71, P = .003). Integrated data analysis revealed 4-miRNA signature-associated genes and pathways. Conclusion: The prognostic 4-miRNA signature in combination with MGMT promoter methylation improved risk stratification with the potential for therapeutic substratification, especially of younger patients.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Mgmt Promoter Methylation ; Glioblastoma ; Mirna ; Prognostic Signature ; Risk Stratification
ISSN (print) / ISBN 2632-2498
e-ISSN 2632-2498
Zeitschrift Neuro-oncology advances
Quellenangaben Band: 2, Heft: 1, Seiten: , Artikelnummer: vdaa137 Supplement: ,
Verlag Oxford University Press
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Research Unit Radiation Cytogenetics (ZYTO)
Institute of Radiation Biology (ISB)
CCG Personalized Radiotherapy in Head and Neck Cancer (KKG-KRT)