Association of hyperglycemia and molecular subclass on survival in IDH-wildtype glioblastoma.
Neurooncol Adv
; 4(1): vdac163, 2022.
Article
em En
| MEDLINE
| ID: mdl-36382106
ABSTRACT
Background:
Hyperglycemia has been associated with worse survival in glioblastoma. Attempts to lower glucose yielded mixed responses which could be due to molecularly distinct GBM subclasses.Methods:
Clinical, laboratory, and molecular data on 89 IDH-wt GBMs profiled by clinical next-generation sequencing and treated with Stupp protocol were reviewed. IDH-wt GBMs were sub-classified into RTK I (Proneural), RTK II (Classical) and Mesenchymal subtypes using whole-genome DNA methylation. Average glucose was calculated by time-weighting glucose measurements between diagnosis and last follow-up.Results:
Patients were stratified into three groups using average glucose tertile one (<100 mg/dL), tertile two (100-115 mg/dL), and tertile three (>115 mg/dL). Comparison across glucose tertiles revealed no differences in performance status (KPS), dexamethasone dose, MGMT methylation, or methylation subclass. Overall survival (OS) was not affected by methylation subclass (P = .9) but decreased with higher glucose (P = .015). Higher glucose tertiles were associated with poorer OS among RTK I (P = .08) and mesenchymal tumors (P = .05), but not RTK II (P = .99). After controlling for age, KPS, dexamethasone, and MGMT status, glucose remained significantly associated with OS (aHR = 5.2, P = .02). Methylation clustering did not identify unique signatures associated with high or low glucose levels. Metabolomic analysis of 23 tumors showed minimal variation across metabolites without differences between molecular subclasses.Conclusion:
Higher average glucose values were associated with poorer OS in RTKI and Mesenchymal IDH-wt GBM, but not RTKII. There were no discernible epigenetic or metabolomic differences between tumors in different glucose environments, suggesting a potential survival benefit to lowering systemic glucose in selected molecular subtypes.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Tipo de estudo:
Guideline
/
Risk_factors_studies
Idioma:
En
Revista:
Neurooncol Adv
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Estados Unidos