title: Promoter methylation of AREG, HOXA11, hMLH1, NDRG2, NPTX2 and Tes genes in glioblastoma.
abstract: Epigenetic alterations alone or in combination with genetic mechanisms play a key role in brain tumorigenesis. Glioblastoma is one of the most common, lethal and poor clinical outcome primary brain tumors with extraordinarily miscellaneous epigenetic alterations profile. The aim of this study was to investigate new potential prognostic epigenetic markers such as AREG, HOXA11, hMLH1, NDRG2, NTPX2 and Tes genes promoter methylation, frequency and value for patients outcome. We examined the promoter methylation status using methylation-specific polymerase chain reaction in 100 glioblastoma tissue samples. The value for clinical outcome was calculated using Kaplan-Meier estimation with log-rank test. DNA promoter methylation was frequent event appearing more than 45 % for gene. AREG and HOXA11 methylation status was significantly associated with patient age. HOXA11 showed the tendency to be associated with patient outcome in glioblastomas. AREG gene promoter methylation showed significant correlation with poor patient outcome. AREG methylation remained significantly associated with patient survival in a Cox multivariate model including MGMT promoter methylation status. This study of new epigenetic targets has shown considerably high level of analyzed genes promoter methylation variability in glioblastoma tissue. AREG gene might be valuable marker for glioblastoma patient survival prognosis, however further analysis is needed to clarify the independence and appropriateness of the marker.
authors.affiliation: Laboratory of Neurooncology and Genetics, Neuroscience Institute, Lithuanian University of Health Sciences, Eiveniu str 4, 50161 Kaunas, Lithuania. dainski@gmail.com
authors.forename: Daina
authors.initials: D
authors.lastname: Skiriutė
authors.forename: Paulina
authors.initials: P
authors.lastname: Vaitkienė
authors.forename: Virginija
authors.initials: V
authors.lastname: Ašmonienė
authors.forename: Giedrius
authors.initials: G
authors.lastname: Steponaitis
authors.forename: Vytenis Pranas
authors.initials: VP
authors.lastname: Deltuva
authors.forename: Arimantas
authors.initials: A
authors.lastname: Tamašauskas
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D066258:Amphiregulin; D014408:Biomarkers, Tumor / Q000235:genetics*; D001932:Brain Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D002097:C-Reactive Protein / Q000235:genetics; D003598:Cytoskeletal Proteins / Q000235:genetics; D019175:DNA Methylation; D066255:EGF Family of Proteins; D005260:Female; D005500:Follow-Up Studies; D005909:Glioblastoma / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D006023:Glycoproteins / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D060588:LIM Domain Proteins / Q000235:genetics; D008297:Male; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D009419:Nerve Tissue Proteins / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D016133:Polymerase Chain Reaction; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics*; D016601:RNA-Binding Proteins; D015996:Survival Rate; D025521:Tumor Suppressor Proteins / Q000235:genetics; D000099153:Pentraxins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D066258:Amphiregulin; D014408:Biomarkers, Tumor; D002097:C-Reactive Protein; D003598:Cytoskeletal Proteins; D066255:EGF Family of Proteins; D006023:Glycoproteins; D018398:Homeodomain Proteins; D036341:Intercellular Signaling Peptides and Proteins; D060588:LIM Domain Proteins; D000070957:MutL Protein Homolog 1; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D016601:RNA-Binding Proteins; D025521:Tumor Suppressor Proteins; D000099153:Pentraxins; C587848:AREG protein, human; C484298:HOXA11 protein, human; C501486:MLH1 protein, human; C466228:NDRG2 protein, human; C429688:TES protein, human