Association of Promoter Methylation of VGF and PGP9.5 with Ovarian Cancer Progression

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dc.contributor.authorBarbosa Quintana, Álvaroes_MX
dc.contributor.creatorBarbosa Quintana, Álvaroes_MX
dc.creatorALVARO BARBOSA QUINTANA; 271483es
dc.date2013
dc.date.accessioned2018-10-18T20:12:51Z
dc.date.available2018-10-18T20:12:51Z
dc.descriptionPurpose:To elucidate the role of biological and clinical impact of aberrant promoter hypermethylation (PH) in ovarian cancer (OC).Experimental Design:PH of PGP9.5, HIC1, AIM1, APC, PAK3, MGMT, KIF1A, CCNA1, ESR1, SSBP2, GSTP1, FKBP4 and VGF were assessed by quantitative methylation specific PCR (QMSP) in a training set. We selected two genes (VGF and PGP9.5) for further QMSP analysis in a larger independent validation (IV) set with available clinical data. Biologic relevance of VGF gene was also evaluated.Results:PH frequency for PGP9.5 and VGF were 85% (316/372) and 43% (158/366) respectively in the IV set of samples while no PH was observed in controls. In 372 OC cases with available follow up, PGP9.5 and VGF PH were correlated with better patient survival [Hazard Ratios (HR) for overall survival (OS) were 0.59 (95% Confidence Intervals (CI) = 0.42-0.84, p = 0.004), and 0.73 (95%CI = 0.55-0.97, p = 0.028) respectively, and for disease specific survival (DSS) were 0.57 (95%CI 0.39-0.82, p = 0.003) and 0.72 (95%CI 0.54-0.96, p = 0.027). In multivariate analysis, VGF PH remained an independent prognostic factor for OS (HR 0.61, 95%CI 0.43-0.86, p<0.005) and DSS (HR 0.58, 95%CI 0.41-0.83, p<0.003). Furthermore, PGP9.5 PH was significantly correlated with lower grade, early stage tumors, and with absence of residual disease. Forced expression of VGF in OC cell lines inhibited cell growth.Conclusions:Our results indicate that VGF and PGP9.5 PH are potential biomarkers for ovarian carcinoma. Confirmatory cohorts with longitudinal follow-up are required in future studies to define the clinical impact of VGF and PGP9.5 PH before clinical application. © 2013 Brait et al.
dc.identifier.doi10.1371/journal.pone.0070878
dc.identifier.issn19326203
dc.identifier.issue9
dc.identifier.urihttp://hdl.handle.net/11285/630310
dc.identifier.volume8
dc.languageeng
dc.relationhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-84884691003&doi=10.1371%2fjournal.pone.0070878&partnerID=40&md5=6462700f19b8f7bb0c059950391eef17
dc.relationInvestigadores
dc.relationEstudiantes
dc.rightsinfo:eu-repo/semantics/openAccess
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0
dc.sourcePLoS ONE
dc.subjectadult
dc.subjectaged
dc.subjectarticle
dc.subjectcancer cell culture
dc.subjectcancer grading
dc.subjectcancer growth
dc.subjectcancer specific survival
dc.subjectcancer staging
dc.subjectcancer survival
dc.subjectcell growth
dc.subjectclinical feature
dc.subjectcontrolled study
dc.subjectDNA methylation
dc.subjectfemale
dc.subjectgene frequency
dc.subjectgene overexpression
dc.subjectgenetic association
dc.subjecthuman
dc.subjecthuman cell
dc.subjectin vitro study
dc.subjectmajor clinical study
dc.subjectovary cancer
dc.subjectoverall survival
dc.subjectPGP9 5 gene
dc.subjectpolymerase chain reaction
dc.subjectpromoter region
dc.subjectsurvival rate
dc.subjectsurvival time
dc.subjectVGF gene
dc.subjectAdult
dc.subjectAged
dc.subjectAzacitidine
dc.subjectBase Sequence
dc.subjectCohort Studies
dc.subjectDisease Progression
dc.subjectDNA Methylation
dc.subjectDNA Primers
dc.subjectFemale
dc.subjectHumans
dc.subjectMiddle Aged
dc.subjectNerve Growth Factors
dc.subjectOvarian Neoplasms
dc.subjectPromoter Regions, Genetic
dc.subjectReal-Time Polymerase Chain Reaction
dc.subjectReverse Transcriptase Polymerase Chain Reaction
dc.subjectUbiquitin Thiolesterase
dc.subject.classification7 INGENIERÍA Y TECNOLOGÍA
dc.titleAssociation of Promoter Methylation of VGF and PGP9.5 with Ovarian Cancer Progression
dc.typeArtículo
refterms.dateFOA2018-10-18T20:12:51Z

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