G6PD as a predictive marker for glioma risk, prognosis and chemosensitivity

Purpose Glucose-6-phosphate dehydrogenase (G6PD) is a key enzyme preventing cells from oxidative damage and has been reported to have tumor-promoting roles. This study aims to comprehensively evaluate the predictive values of G6PD on brain tumor risk, prognosis and chemo-resistance. Methods A retros...

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Bibliographic Details
Published in:Journal of neuro-oncology 2018-09, Vol.139 (3), p.661-670
Main Authors: Yang, Chin-An, Huang, Hsi-Yuan, Lin, Cheng-Li, Chang, Jan-Gowth
Format: Article
Language:English
Subjects:
Bioinformatics
Bortezomib
Brain cancer
Brain tumors
Chemotherapy
Clinical Study
Gemcitabine
Genomes
Glioblastoma
Glioma
Glucosephosphate dehydrogenase
Medical prognosis
Medicine
Medicine & Public Health
MSH2 protein
MSH6 protein
Neurology
Oncology
Prognosis
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Summary:Purpose Glucose-6-phosphate dehydrogenase (G6PD) is a key enzyme preventing cells from oxidative damage and has been reported to have tumor-promoting roles. This study aims to comprehensively evaluate the predictive values of G6PD on brain tumor risk, prognosis and chemo-resistance. Methods A retrospective 13-year cohort study analyzing cancer risk using the Taiwan National Health Insurance Research Database (4066 G6PD deficiency patients and 16,264 controls) was conducted. Furthermore, RNAseq and clinical data of grade II–III glioma (LGG, n = 515) and glioblastoma (GBM, n = 155) were downloaded from The Cancer Genome Atlas (TCGA) and analyzed. Bioinformatics methods were applied to build a glioma prognostication model and to predict response to chemotherapy based on tumor G6PD -related gene expressions. The predicted results were validated in another glioma cohort GSE 16011 and in KALS1 cell line. Results G6PD-dificient patients were found to have an increased risk for cancers, especially for brain tumor (adjusted hazard ratio (HR) 10.5, 95% CI 1.03–7.60). Furthermore, higher tumor G6PD expression was associated with poor patient survival in LGG, but not in GBM. A prognostication model using expression levels of G6PD and 9 related genes ( PSMA2, PSMB8, SHFM1, GSS, GSTK1, MGST2, POLD3, MSH2, MSH6 ) could independently predict LGG patient survival. Boosted decision tree analysis on 213 cancer cell line database revealed predictive values of G6PD expression on response to gemcitabine and bortezomib. Knockdown of G6PD in KALS1 cell line enhanced its sensitivity to both chemotherapeutic agents. Conclusions Our study suggests that G6PD could be a marker predicting glioma risk, prognosis and chemo-sensitivity.
ISSN:0167-594X
1573-7373
DOI:10.1007/s11060-018-2911-8