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Global and gene-specific DNA methylation pattern discriminates cholecystitis from gallbladder cancer patients in Chile.

ABSTRACT: The aim of the study was to evaluate the use of global and gene-specific DNA methylation changes as potential biomarkers for gallbladder cancer (GBC) in a cohort from Chile.DNA methylation was analyzed through an ELISA-based technique and quantitative methylation-specific PCR.Global DNA Methylation Index (p = 0.02) and promoter methylation of SSBP2 (p = 0.01) and ESR1 (p = 0.05) were significantly different in GBC when compared with cholecystitis. Receiver curve operator analysis revealed promoter methylation of APC, CDKN2A, ESR1, PGP9.5 and SSBP2, together with the Global DNA Methylation Index, had 71% sensitivity, 95% specificity, a 0.97 area under the curve and a positive predictive value of 90%.Global and gene-specific DNA methylation may be useful biomarkers for GBC clinical assessment.

SUBMITTER: Kagohara LT

PROVIDER: S-EPMC4332836 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Global and gene-specific DNA methylation pattern discriminates cholecystitis from gallbladder cancer patients in Chile.

Kagohara Luciane Tsukamoto LT Schussel Juliana L JL Subbannayya Tejaswini T Sahasrabuddhe Nandini N Lebron Cynthia C Brait Mariana M Maldonado Leonel L Valle Blanca L BL Pirini Francesca F Jahuira Martha M Lopez Jaime J Letelier Pablo P Brebi-Mieville Priscilla P Ili Carmen C Pandey Akhilesh A Chatterjee Aditi A Sidransky David D Guerrero-Preston Rafael R

Future oncology (London, England) 20140728 2

<h4>Aim</h4>The aim of the study was to evaluate the use of global and gene-specific DNA methylation changes as potential biomarkers for gallbladder cancer (GBC) in a cohort from Chile.<h4>Material & methods</h4>DNA methylation was analyzed through an ELISA-based technique and quantitative methylation-specific PCR.<h4>Results</h4>Global DNA Methylation Index (p = 0.02) and promoter methylation of SSBP2 (p = 0.01) and ESR1 (p = 0.05) were significantly different in GBC when compared with cholecys ...[more]

PMID: 25066711

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Project description:Objective: Obesity and obesity-related metabolic diseases are characterized by gut microbiota and epigenetic alterations. Recent insight has suggested the existence of a crosstalk between the gut microbiome and the epigenome. However, the possible link between alterations in gut microbiome composition and epigenetic marks in obesity has been not explored yet. The aim of this work is to establish a link between the gut microbiota and the global DNA methylation profile in a group of obese subjects and to report potential candidate genes that could be epigenetically regulated by gut microbiota in adipose tissue. Methods: Gut microbiota composition was analyzed in DNA stool samples from 45 obese subjects by 16S ribosomal RNA (rRNA) gene sequencing. Twenty patients were selected based on their Bacteroidetes-to-Firmicutes ratio (BFR): HighBFR group (BFR > 2.5, n = 10) and LowBFR group (BFR < 1.2, n = 10). Genome-wide analysis of DNA methylation pattern in both whole blood and visceral adipose tissue of these selected patients was performed with an Infinium EPIC BeadChip array-based platform. Gene expression analysis of candidate genes was done in adipose tissue by real-time quantitative PCR. Results: Genome-wide analysis of DNA methylation revealed a completely different DNA methylome pattern in both blood and adipose tissue in the low BFR group vs. the high BFR group. Two hundred fifty-eight genes were differentially methylated in both blood and adipose tissue, of which several potential candidates were selected for gene expression analysis. We found that in adipose tissue, both HDAC7 and IGF2BP2 were hypomethylated and overexpressed in the low BFR group compared with the high BFR group. β values of both genes significantly correlated with the BFR ratio and the relative abundance of Bacteroidetes and/or Firmicutes. Conclusions: In this study, we demonstrate that the DNA methylation status is associated with gut microbiota composition in obese subjects and that the expression levels of candidate genes implicated in glucose and energy homeostasis (e.g., HDAC7 and IGF2BP2) could be epigenetically regulated by gut bacterial populations in adipose tissue.

Dataset Information

Global and gene-specific DNA methylation pattern discriminates cholecystitis from gallbladder cancer patients in Chile.

Publications

Global and gene-specific DNA methylation pattern discriminates cholecystitis from gallbladder cancer patients in Chile.

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