Medizinische Universität Graz - Research portal
Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Brawanski, KR; Sprung, S; Freyschlag, CF; Hoeftberger, R; Ströbel, T; Haybaeck, J; Thomé, C; Manzl, C; Birkl-Toeglhofer, AM.
Influence of MMR, MGMT Promotor Methylation and Protein Expression on Overall and Progression-Free Survival in Primary Glioblastoma Patients Treated with Temozolomide.
Int J Mol Sci. 2023; 24(7):
Doi: 10.3390/ijms24076184
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Web of Science
PubMed
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- Leading authors Med Uni Graz
- Birkl-Töglhofer Anna Maria
- Co-authors Med Uni Graz
- Haybäck Johannes
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- Abstract:
- Glioblastoma is the most common malignant brain tumor in adults. Standard treatment includes tumor resection, radio-chemotherapy and adjuvant chemotherapy with temozolomide (TMZ). TMZ methylates DNA, whereas O6-methylguanine DNA methyltransferase (MGMT) counteracts TMZ effects by removing the intended proteasomal degradation signal. Non-functional MGMT mediates the mismatch repair (MMR) system, leading to apoptosis after futile repair attempts. This study investigated the associations between MGMT promoter methylation, MGMT and MMR protein expression, and their effect on overall survival (OS) and progression-free survival (PFS) in patients with glioblastoma. MGMT promoter methylation was assessed in 42 treatment-naïve patients with glioblastoma WHO grade IV by pyrosequencing. MGMT and MMR protein expression was analyzed using immunohistochemistry. MGMT promoter methylation was present in 52%, whereas patients <70 years of age revealed a significantly longer OS using a log-rank test and a significance threshold of p ≤ 0.05. MGMT protein expression and methylation status showed no correlation. MMR protein expression was present in all patients independent of MGMT status and did not influence OS and PFS. Overall, MGMT promoter methylation implicates an improved OS in patients with glioblastoma aged <70 years. In the elderly, the extent of surgery has an impact on OS rather than the MGMT promoter methylation or protein expression.
- Find related publications in this database (using NLM MeSH Indexing)
- Adult - administration & dosage
- Aged - administration & dosage
- Humans - administration & dosage
- Temozolomide - pharmacology, therapeutic use
- Glioblastoma - drug therapy, genetics
- Progression-Free Survival - administration & dosage
- Antineoplastic Agents, Alkylating - pharmacology, therapeutic use
- Dacarbazine - pharmacology, therapeutic use
- Methylation - administration & dosage
- DNA Mismatch Repair - administration & dosage
- DNA Modification Methylases - genetics, metabolism
- Brain Neoplasms - drug therapy, genetics, metabolism
- O(6)-Methylguanine-DNA Methyltransferase - genetics
- DNA Repair Enzymes - genetics, metabolism
- DNA Methylation - administration & dosage
- Tumor Suppressor Proteins - genetics, metabolism
- Find related publications in this database (Keywords)
- glioblastoma
- MGMT promoter methylation
- MGMT protein expression
- mismatch repair
- temozolomide
- immunohistochemical analysis