title: The contrasting epigenetic role of RUNX3 when compared with that of MGMT and TIMP3 in glioblastoma multiforme clinical outcomes.
abstract: 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).
authors.affiliation: Molecular Oncology and Imaging Program, Molecular Imaging Group, IDIS, Complejo Hospitalario Universitario, 15706 Santiago de Compostela, Spain. Electronic address: uxiasaraiba@gmail.com.
authors.forename: Uxia
authors.initials: U
authors.lastname: Saraiva-Esperón
authors.affiliation: Radiology and Physical Medicine Department, Faculty of Medicine, Nuclear Medicine Service, Complejo Hospitalario Universitario, Molecular Imaging Group, IDIS, Fundación Tejerina, 15706 Santiago de Compostela, Spain. Electronic address: alvaro.ruibal.morell@sergas.es.
authors.forename: Alvaro
authors.initials: A
authors.lastname: Ruibal
authors.affiliation: Molecular Oncology and Imaging Program, Molecular Imaging Group, IDIS, Complejo Hospitalario Universitario, 15706 Santiago de Compostela, Spain. Electronic address: michel.herranz.carnero@sergas.es.
authors.forename: Michel
authors.initials: M
authors.lastname: Herranz
mesh_terms: D000328:Adult; D000368:Aged; D050677:Core Binding Factor Alpha 3 Subunit / Q000235:genetics*; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000235:genetics*; D045643:DNA Repair Enzymes / Q000235:genetics*; D044127:Epigenesis, Genetic / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005909:Glioblastoma / Q000235:genetics* / Q000401:mortality / Q000503:physiopathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011379:Prognosis; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D050677:Core Binding Factor Alpha 3 Subunit; C493729:Runx3 protein, human; C088390:TIMP3 protein, human; D019717:Tissue Inhibitor of Metalloproteinase-3; D025521:Tumor Suppressor Proteins; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes
keywords: Epigenetics; Glioblastoma; MGMT; Outcome; RUNX3; TIMP3