Authors: Sheila C.S. Lima, Héctor Hernández-Vargas, Tatiana Simão, Geoffroy Durand, Cleber Dario Pinto Kruel, Florence Le Calvez-Kelm, Luis Felipe Ribeiro Pinto and Zdenko Herceg

Sheila C.S. Lima

International Agency for Research on Cancer (IARC); Lyon, France; Divisão de Genética, Coordenação de Pesquisa; Instituto Nacional de Câncer; Rio de Janeiro, Brazil

Héctor Hernández-Vargas

International Agency for Research on Cancer (IARC); Lyon, France

Tatiana Simão

Divisão de Genética, Coordenação de Pesquisa; Instituto Nacional de Câncer; Rio de Janeiro, Brazil; Departamento de Bioquímica, Universidade do Estado do Rio de Janeiro; Instituto de Biologia Roberto Alcantara Gomes; Rio de Janeiro, Brazil

Geoffroy Durand

International Agency for Research on Cancer (IARC); Lyon, France

Cleber Dario Pinto Kruel

Departamento de Cirurgia Gástrica, Faculdade de Ciências Médicas; Hospital da Clínicas de Porto Alegre; Rio Grande do Sul, Brazil

Florence Le Calvez-Kelm

International Agency for Research on Cancer (IARC); Lyon, France

Luis Felipe Ribeiro Pinto

Divisão de Genética, Coordenação de Pesquisa; Instituto Nacional de Câncer; Rio de Janeiro, Brazil; Departamento de Bioquímica, Universidade do Estado do Rio de Janeiro; Instituto de Biologia Roberto Alcantara Gomes; Rio de Janeiro, Brazil

Zdenko Herceg

Corresponding author: herceg@iarc.fr
International Agency for Research on Cancer (IARC); Lyon, France

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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.