The contrasting epigenetic role of RUNX3 when compared with that of MGMT and TIMP3 in glioblastoma multiforme clinical outcomes

摘要

Glioblastoma multiforme (GBM) is the most frequent and malignant astrocytic glioma in the adult, with a survival rate at 5 years less than 5%. In the GBM pathogenesis, the importance of genes methylation involved in cell cycle, tumor suppression, DNA repair and genome integrity, as well as tumor invasion and apoptosis has been described. We analyzed epigenetic regulation involvement of two genes related with apoptosis: TIMP3 and RUNX3 in order to define a clinical profile and compare with the most studied gene in GBM: MGMT. Eighty samples from GBM patients were evaluated by methylation specific PCR (MSP). Data from each patient were collected from medical histories to relate survival rates with gene methylation patterns. Methylation percentages obtained were: MGMT 45%, RUNX3 30% and TIMP3 28%. The study of MGMT methylation had prognostic value in patients with glioblastoma multiforme because at 8 months, 28% of patients survived with the gene methylated, while none of them lived with the gene unmethylated (P = 0.016). RUNX3 behavior was opposite to TIMP3 and MGMT. TIMP3action, in terms of patient's survival, was similar to that observed with MGMT, percentage of patients surviving at 8 months with the gene methylated was 27%, compared with 7% of those with the unmethylated gene; there being a tendency to statistical significance (p = 0.09). (C) 2014 Elsevier B.V. All rights reserved.