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Published on: October 4, 2019
Lower MGMT expression predicts better prognosis in proneural-like glioblastoma
Zhi-Cheng He1, Yi-Fang Ping1, Sen-Lin Xu1
1Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical UniversityChongqing 400038, China; Key Laboratory of Tumor Immunopathology of Ministry of Education of China, Third Military Medical UniversityChongqing 400038, China.
Objective:
To investigate the expression and significance of MGMT in different molecular subtypes of glioblastoma (GBM), and to evaluate the important role of MGMT and P53 in predicting the prognosis of GBM patients.
Methods:
MGMT expression was detected by immunohistochemical staining in 72 cases of GBM which had been classified as three molecular subtypes. The relationship between MGMT and P53, an important molecule for identification of proneural-like GBM, were further analyzed. The association between MGMT and patients' prognosis was analyzed with Kaplan-Meier method, which was further validated by the data from 513 cases of GBM in the TCGA database.
Results:
MGMT expression was lower in proneural-like subtype in 72 GBM cases (p < 0.001), and was negatively correlated with P53 (r=-0. 6203, p < 0.001). This results was also verified by a validation group of 87 GBM cases (r=-0. 2950, p < 0.001). Interestingly, low expression of MGMT predicted a better outcome in proneurallike subtype or P53 high-expression group (p < 0.05) but not in non-proneural-like subtype and P53 low-expression group. All of these results were verified by the data from TCGA database.
Conclusion:
MGMT can be used as an independent prognostic factor and plays an important role in molecular typing and diagnosis of GBM by combination with proneural-like subtype marker P53.
Insights
O-6-methylguanine-DNA methyltransferase (MGMT) expression is a key prognostic factor in glioblastoma (GBM). Low MGMT expression predicts better outcomes in specific GBM subtypes, highlighting its role in diagnosis.
Area of Science:
- Neuro-oncology
- Molecular diagnostics
- Cancer biomarkers
Background:
- Glioblastoma (GBM) is an aggressive brain tumor with varied molecular subtypes.
- O-6-methylguanine-DNA methyltransferase (MGMT) and P53 are critical in GBM pathogenesis and prognosis.
- Understanding MGMT's role across GBM subtypes is crucial for targeted therapy and improved patient outcomes.
Purpose of the Study:
- To investigate MGMT expression and its prognostic significance in distinct GBM molecular subtypes.
- To evaluate the combined role of MGMT and P53 in predicting GBM patient prognosis.
- To explore MGMT's utility in molecular subtyping and diagnosis of GBM.
Main Methods:
- Immunohistochemical staining of MGMT in 72 GBM cases across three molecular subtypes.
- Analysis of the correlation between MGMT and P53 expression.
- Kaplan-Meier survival analysis for MGMT and prognosis association.
- Validation using TCGA database (513 GBM cases).
Main Results:
- MGMT expression was significantly lower in the proneural-like GBM subtype (p < 0.001).
- MGMT expression showed a negative correlation with P53 (r=-0.6203, p < 0.001), validated in a separate cohort.
- Low MGMT expression correlated with better prognosis in the proneural-like/P53-high subgroup, but not in others.
Conclusions:
- MGMT serves as an independent prognostic factor in glioblastoma.
- MGMT, in conjunction with P53, aids in molecular subtyping and diagnosis of GBM.
- These findings underscore the importance of MGMT in GBM patient stratification and treatment strategies.
