TY - JOUR
T1 - Association of hyperglycemia and molecular subclass on survival in IDH-wildtype glioblastoma
AU - Liu, Elisa K.
AU - Vasudevaraja, Varshini
AU - Sviderskiy, Vladislav O.
AU - Feng, Yang
AU - Tran, Ivy
AU - Serrano, Jonathan
AU - Cordova, Christine
AU - Kurz, Sylvia C.
AU - Golfinos, John G.
AU - Sulman, Erik P.
AU - Orringer, Daniel A.
AU - Placantonakis, Dimitris
AU - Possemato, Richard
AU - Snuderl, Matija
N1 - Funding Information:
Funding The study was in part supported by NIH grants R21-EB025406, R01-CA226527. DNA methylation profiling was supported by the Friedberg Charitable Foundation and the Gray Family Foundation.
Publisher Copyright:
© 2022 The Author(s). Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.
PY - 2022/1/1
Y1 - 2022/1/1
N2 - 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.
AB - 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.
KW - glioblastoma
KW - glucose
KW - hyperglycemia
KW - methylation
KW - subclass
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U2 - 10.1093/noajnl/vdac163
DO - 10.1093/noajnl/vdac163
M3 - Article
AN - SCOPUS:85145386484
SN - 2632-2498
VL - 4
JO - Neuro-Oncology Advances
JF - Neuro-Oncology Advances
IS - 1
M1 - vdac163
ER -