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

Mariana Brait, Leonel Maldonado, Maartje Noordhuis, Shahnaz Begum, Myriam Loyo, Maria Luana Poeta, Alvaro Barbosa, Vito M. Fazio, Roberto Angioli, Carla Rabitti, Luigi Marchionni, Pauline de Graeff, Ate G J van der Zee, G. Bea A Wisman, David Sidransky, Mohammad O. Hoque

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Abstract

Purpose: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

Original languageEnglish (US)
Article numbere70878
JournalPLoS One
Volume8
Issue number9
DOIs
StatePublished - Sep 27 2013
Externally publishedYes

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Methylation
ovarian neoplasms
methylation
Ovarian Neoplasms
Hazards
Genes
promoter regions
confidence interval
Confidence Intervals
Survival
Design of experiments
Polymerase Chain Reaction
Research Design
Multivariate Analysis
multivariate analysis
genes
experimental design
tacrolimus binding protein 4

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Brait, M., Maldonado, L., Noordhuis, M., Begum, S., Loyo, M., Poeta, M. L., ... Hoque, M. O. (2013). Association of Promoter Methylation of VGF and PGP9.5 with Ovarian Cancer Progression. PLoS One, 8(9), [e70878]. https://doi.org/10.1371/journal.pone.0070878

Association of Promoter Methylation of VGF and PGP9.5 with Ovarian Cancer Progression. / Brait, Mariana; Maldonado, Leonel; Noordhuis, Maartje; Begum, Shahnaz; Loyo, Myriam; Poeta, Maria Luana; Barbosa, Alvaro; Fazio, Vito M.; Angioli, Roberto; Rabitti, Carla; Marchionni, Luigi; de Graeff, Pauline; van der Zee, Ate G J; Wisman, G. Bea A; Sidransky, David; Hoque, Mohammad O.

In: PLoS One, Vol. 8, No. 9, e70878, 27.09.2013.

Research output: Contribution to journalArticle

Brait, M, Maldonado, L, Noordhuis, M, Begum, S, Loyo, M, Poeta, ML, Barbosa, A, Fazio, VM, Angioli, R, Rabitti, C, Marchionni, L, de Graeff, P, van der Zee, AGJ, Wisman, GBA, Sidransky, D & Hoque, MO 2013, 'Association of Promoter Methylation of VGF and PGP9.5 with Ovarian Cancer Progression', PLoS One, vol. 8, no. 9, e70878. https://doi.org/10.1371/journal.pone.0070878
Brait, Mariana ; Maldonado, Leonel ; Noordhuis, Maartje ; Begum, Shahnaz ; Loyo, Myriam ; Poeta, Maria Luana ; Barbosa, Alvaro ; Fazio, Vito M. ; Angioli, Roberto ; Rabitti, Carla ; Marchionni, Luigi ; de Graeff, Pauline ; van der Zee, Ate G J ; Wisman, G. Bea A ; Sidransky, David ; Hoque, Mohammad O. / Association of Promoter Methylation of VGF and PGP9.5 with Ovarian Cancer Progression. In: PLoS One. 2013 ; Vol. 8, No. 9.
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abstract = "Purpose: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",
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AU - Brait, Mariana

AU - Maldonado, Leonel

AU - Noordhuis, Maartje

AU - Begum, Shahnaz

AU - Loyo, Myriam

AU - Poeta, Maria Luana

AU - Barbosa, Alvaro

AU - Fazio, Vito M.

AU - Angioli, Roberto

AU - Rabitti, Carla

AU - Marchionni, Luigi

AU - de Graeff, Pauline

AU - van der Zee, Ate G J

AU - Wisman, G. Bea A

AU - Sidransky, David

AU - Hoque, Mohammad O.

PY - 2013/9/27

Y1 - 2013/9/27

N2 - Purpose: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

AB - Purpose: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

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