The prognostic significance of whole blood global and specific DNA methylation levels in gastric adenocarcinoma

Mansour S. Al-Moundhri, Maryam Al-Nabhani, Letizia Tarantini, Andrea Baccarelli, Jennifer A. Rusiecki

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Background: Epigenetics, particularly DNA methylation, has recently been elucidated as important in gastric cancer (GC) initiation and progression. We investigated the clinical and prognostic importance of whole blood global and site-specific DNA methylation in GC. Methods: Genomic DNA was extracted from the peripheral blood of 105 Omani GC patients at diagnosis. DNA methylation was quantified by pyrosequencing of global DNA and specific gene promoter regions at 5 CpG sites for CDH1, 7 CpG sites for p16, 4 CpG sites for p53, and 3 CpG sites for RUNX3. DNA methylation levels in patients were categorized into low, medium, and high tertiles. Associations between methylation level category and clinicopathological features were evaluated using x2 tests. Survival analyses were carried out using the Kaplan-Meier method and log rank test. A backward conditional Cox proportional hazards regression model was used to identify independent predictors of survival. Results: Older GC patients had increased methylation levels at specific CpG sites within the CDH1, p53, and RUNX-3 promoters. Male gender was significantly associated with reduced global and increased site-specific DNA methylation levels in CDH1, p16, and p53 promoters. Global DNA low methylation level was associated with better survival on univariate analysis. Patients with high and medium methylation vs. low methylation levels across p16 promoter CpG sites, site 2 in particular, had better survival. Multivariate analysis showed that global DNA hypermethylation was a significant independent predictor of worse survival (hazard ratio (HR) = 2.0, 95% CI: 1.1-3.8; p = 0.02) and high methylation mean values across p16 promoter sites 1-7 were associated with better survival with HR of 0.3 (95% CI, 0.1-0.8; p = 0.02) respectively. Conclusions: Analysis of global and site-specific DNA methylation in peripheral blood by pyrosequencing provides quantitative DNA methylation values that may serve as important prognostic indicators.

Original languageEnglish
Article numbere15585
JournalPLoS One
Volume5
Issue number12
DOIs
Publication statusPublished - Dec 1 2010

Fingerprint

DNA methylation
DNA Methylation
Methylation
adenocarcinoma
Stomach
stomach
Adenocarcinoma
methylation
Blood
stomach neoplasms
blood
promoter regions
Stomach Neoplasms
Survival
Hazards
DNA
Genetic Promoter Regions
epigenetics
multivariate analysis
Survival Analysis

ASJC Scopus subject areas

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

Cite this

The prognostic significance of whole blood global and specific DNA methylation levels in gastric adenocarcinoma. / Al-Moundhri, Mansour S.; Al-Nabhani, Maryam; Tarantini, Letizia; Baccarelli, Andrea; Rusiecki, Jennifer A.

In: PLoS One, Vol. 5, No. 12, e15585, 01.12.2010.

Research output: Contribution to journalArticle

Al-Moundhri, Mansour S. ; Al-Nabhani, Maryam ; Tarantini, Letizia ; Baccarelli, Andrea ; Rusiecki, Jennifer A. / The prognostic significance of whole blood global and specific DNA methylation levels in gastric adenocarcinoma. In: PLoS One. 2010 ; Vol. 5, No. 12.
@article{74b88b442c32437e80723063bb1981ce,
title = "The prognostic significance of whole blood global and specific DNA methylation levels in gastric adenocarcinoma",
abstract = "Background: Epigenetics, particularly DNA methylation, has recently been elucidated as important in gastric cancer (GC) initiation and progression. We investigated the clinical and prognostic importance of whole blood global and site-specific DNA methylation in GC. Methods: Genomic DNA was extracted from the peripheral blood of 105 Omani GC patients at diagnosis. DNA methylation was quantified by pyrosequencing of global DNA and specific gene promoter regions at 5 CpG sites for CDH1, 7 CpG sites for p16, 4 CpG sites for p53, and 3 CpG sites for RUNX3. DNA methylation levels in patients were categorized into low, medium, and high tertiles. Associations between methylation level category and clinicopathological features were evaluated using x2 tests. Survival analyses were carried out using the Kaplan-Meier method and log rank test. A backward conditional Cox proportional hazards regression model was used to identify independent predictors of survival. Results: Older GC patients had increased methylation levels at specific CpG sites within the CDH1, p53, and RUNX-3 promoters. Male gender was significantly associated with reduced global and increased site-specific DNA methylation levels in CDH1, p16, and p53 promoters. Global DNA low methylation level was associated with better survival on univariate analysis. Patients with high and medium methylation vs. low methylation levels across p16 promoter CpG sites, site 2 in particular, had better survival. Multivariate analysis showed that global DNA hypermethylation was a significant independent predictor of worse survival (hazard ratio (HR) = 2.0, 95{\%} CI: 1.1-3.8; p = 0.02) and high methylation mean values across p16 promoter sites 1-7 were associated with better survival with HR of 0.3 (95{\%} CI, 0.1-0.8; p = 0.02) respectively. Conclusions: Analysis of global and site-specific DNA methylation in peripheral blood by pyrosequencing provides quantitative DNA methylation values that may serve as important prognostic indicators.",
author = "Al-Moundhri, {Mansour S.} and Maryam Al-Nabhani and Letizia Tarantini and Andrea Baccarelli and Rusiecki, {Jennifer A.}",
year = "2010",
month = "12",
day = "1",
doi = "10.1371/journal.pone.0015585",
language = "English",
volume = "5",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "12",

}

TY - JOUR

T1 - The prognostic significance of whole blood global and specific DNA methylation levels in gastric adenocarcinoma

AU - Al-Moundhri, Mansour S.

AU - Al-Nabhani, Maryam

AU - Tarantini, Letizia

AU - Baccarelli, Andrea

AU - Rusiecki, Jennifer A.

PY - 2010/12/1

Y1 - 2010/12/1

N2 - Background: Epigenetics, particularly DNA methylation, has recently been elucidated as important in gastric cancer (GC) initiation and progression. We investigated the clinical and prognostic importance of whole blood global and site-specific DNA methylation in GC. Methods: Genomic DNA was extracted from the peripheral blood of 105 Omani GC patients at diagnosis. DNA methylation was quantified by pyrosequencing of global DNA and specific gene promoter regions at 5 CpG sites for CDH1, 7 CpG sites for p16, 4 CpG sites for p53, and 3 CpG sites for RUNX3. DNA methylation levels in patients were categorized into low, medium, and high tertiles. Associations between methylation level category and clinicopathological features were evaluated using x2 tests. Survival analyses were carried out using the Kaplan-Meier method and log rank test. A backward conditional Cox proportional hazards regression model was used to identify independent predictors of survival. Results: Older GC patients had increased methylation levels at specific CpG sites within the CDH1, p53, and RUNX-3 promoters. Male gender was significantly associated with reduced global and increased site-specific DNA methylation levels in CDH1, p16, and p53 promoters. Global DNA low methylation level was associated with better survival on univariate analysis. Patients with high and medium methylation vs. low methylation levels across p16 promoter CpG sites, site 2 in particular, had better survival. Multivariate analysis showed that global DNA hypermethylation was a significant independent predictor of worse survival (hazard ratio (HR) = 2.0, 95% CI: 1.1-3.8; p = 0.02) and high methylation mean values across p16 promoter sites 1-7 were associated with better survival with HR of 0.3 (95% CI, 0.1-0.8; p = 0.02) respectively. Conclusions: Analysis of global and site-specific DNA methylation in peripheral blood by pyrosequencing provides quantitative DNA methylation values that may serve as important prognostic indicators.

AB - Background: Epigenetics, particularly DNA methylation, has recently been elucidated as important in gastric cancer (GC) initiation and progression. We investigated the clinical and prognostic importance of whole blood global and site-specific DNA methylation in GC. Methods: Genomic DNA was extracted from the peripheral blood of 105 Omani GC patients at diagnosis. DNA methylation was quantified by pyrosequencing of global DNA and specific gene promoter regions at 5 CpG sites for CDH1, 7 CpG sites for p16, 4 CpG sites for p53, and 3 CpG sites for RUNX3. DNA methylation levels in patients were categorized into low, medium, and high tertiles. Associations between methylation level category and clinicopathological features were evaluated using x2 tests. Survival analyses were carried out using the Kaplan-Meier method and log rank test. A backward conditional Cox proportional hazards regression model was used to identify independent predictors of survival. Results: Older GC patients had increased methylation levels at specific CpG sites within the CDH1, p53, and RUNX-3 promoters. Male gender was significantly associated with reduced global and increased site-specific DNA methylation levels in CDH1, p16, and p53 promoters. Global DNA low methylation level was associated with better survival on univariate analysis. Patients with high and medium methylation vs. low methylation levels across p16 promoter CpG sites, site 2 in particular, had better survival. Multivariate analysis showed that global DNA hypermethylation was a significant independent predictor of worse survival (hazard ratio (HR) = 2.0, 95% CI: 1.1-3.8; p = 0.02) and high methylation mean values across p16 promoter sites 1-7 were associated with better survival with HR of 0.3 (95% CI, 0.1-0.8; p = 0.02) respectively. Conclusions: Analysis of global and site-specific DNA methylation in peripheral blood by pyrosequencing provides quantitative DNA methylation values that may serve as important prognostic indicators.

UR - http://www.scopus.com/inward/record.url?scp=78650817214&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=78650817214&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0015585

DO - 10.1371/journal.pone.0015585

M3 - Article

C2 - 21203466

AN - SCOPUS:78650817214

VL - 5

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 12

M1 - e15585

ER -