title: Identification of a DNA methylome signature of esophageal squamous cell carcinoma and potential epigenetic biomarkers.
abstract: Esophageal squamous cell carcinoma (ESCC) is believed to arise from esophageal mucosa through accumulation of both genetic and epigenetic changes. DNA methylation is a critical epigenetic mechanism involved in key cellular processes and its deregulation has been linked to many human cancers, including ESCC. The aim of this study is to examine the global deregulation of methylation states in ESCC and identify potential early biomarkers. With this purpose, we performed a bead array analysis of more than 800 cancer-related genes in ten ESCC samples, ten matched surrounding tissues and four esophageal mucosa from healthy individuals. Pyrosequencing was used for validation of DNA methylation changes in up to 106 cases and 27 controls. A total of 37 CpG sites were found to be differentially methylated between tumors and surrounding tissues. These CpG sites were significantly enriched in genes related to several pathways including IL-10 anti-inflammatory signaling pathway and cell communication pathway. In addition, by comparing with healthy esophageal mucosa, we identified TFF1 gene as a potential early marker of ESCC. This is the first study to address methylation changes in ESCC in a large set of genes. Methylome analysis is shown as a sensitive and powerful tool to identify molecular players in ESCC. These data should prove to be the reference for future studies identifying potential biomarkers and molecular targets in ESCC.
authors.affiliation: International Agency for Research on Cancer, Lyon, France.
authors.forename: Sheila C S
authors.initials: SC
authors.lastname: Lima
authors.forename: Héctor
authors.initials: H
authors.lastname: Hernández-Vargas
authors.forename: Tatiana
authors.initials: T
authors.lastname: Simão
authors.forename: Geoffroy
authors.initials: G
authors.lastname: Durand
authors.forename: Cleber Dario Pinto
authors.initials: CD
authors.lastname: Kruel
authors.forename: Florence
authors.initials: F
authors.lastname: Le Calvez-Kelm
authors.forename: Luis Felipe
authors.initials: LF
authors.lastname: Ribeiro Pinto
authors.forename: Zdenko
authors.initials: Z
authors.lastname: Herceg
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D018899:CpG Islands; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D004938:Esophageal Neoplasms / Q000235:genetics*; D005819:Genetic Markers; D006801:Humans; D011401:Promoter Regions, Genetic; D017422:Sequence Analysis, DNA; D000071163:Trefoil Factor-1; D025521:Tumor Suppressor Proteins / Q000737:chemistry / Q000235:genetics*
chemical_list: D005819:Genetic Markers; C051838:TFF1 protein, human; D000071163:Trefoil Factor-1; D025521:Tumor Suppressor Proteins