Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/178641
Title: Follow-Up Study Confirms the Presence of Gastric Cancer DNA Methylation Hallmarks in High-Risk Precursor Lesions
Author: Gómez, Antonio
Pato, Miguel L.
Bujanda, Luis
Sala Serra, Núria
Companioni Nápoles, Osmel
Cosme, Ángel
Tufano, Martina
Hanly, David J.
García, Nadia
Sanz Anquela, José Miguel
Gisbert, Javier P.
López, Consol
Elizalde, J. Ignasi
Cuatrecasas Freixas, Miriam
Andreu, Victoria
Paules, María José
Martín Arranz, María Dolores
Ortega, Luis
Poves, Elvira
Barrio, Jesús
Torres, María Ángeles
Muñoz, Guillermo
Ferrández, Ángel
Ramírez Lázaro, María José
Lario, Sergio
González, Carlos A.
Esteller, Manel
Berdasco, María
Keywords: Càncer d'estómac
Helicobacter pylori
Stomach cancer
Helicobacter pylori
Issue Date: 2-Jun-2021
Publisher: MDPI
Abstract: Intestinal metaplasia confers an increased risk of progression to gastric cancer. However, some intestinal metaplasia patients do not develop cancer. The development of robust molecular biomarkers to stratify patients with advanced gastric precursor lesions at risk of cancer progression will contribute to guiding programs for prevention. Starting from a genome-wide methylation study, we have simplified the detection method regarding candidate-methylation tests to improve their applicability in the clinical environment. We identified CpG methylation at the ZNF793 and RPRM promoters as a common event in intestinal metaplasia and intestinal forms of gastric cancer. Furthermore, we also showed that Helicobacter pylori infection influences DNA methylation in early precursor lesions but not in intestinal metaplasia, suggesting that therapeutic strategies to prevent epigenome reprogramming toward a cancer signature need to be adopted early in the precursor cascade. To adopt prevention strategies in gastric cancer, it is imperative to develop robust biomarkers with acceptable costs and feasibility in clinical practice to stratified populations according to risk scores. With this aim, we applied an unbiased genome-wide CpG methylation approach to a discovery cohort composed of gastric cancer (n = 24), and non-malignant precursor lesions (n = 64). Then, candidate-methylation approaches were performed in a validation cohort of precursor lesions obtained from an observational longitudinal study (n = 264), with a 12-year follow-up to identify repression or progression cases. H. pylori stratification and histology were considered to determine their influence on the methylation dynamics. As a result, we ascertained that intestinal metaplasia partially recapitulates patterns of aberrant methylation of intestinal type of gastric cancer, independently of the H. pylori status. Two epigenetically regulated genes in cancer, RPRM and ZNF793, consistently showed increased methylation in intestinal metaplasia with respect to earlier precursor lesions. In summary, our result supports the need to investigate the practical utilities of the quantification of DNA methylation in candidate genes as a marker for disease progression. In addition, the H. pylori-dependent methylation in intestinal metaplasia suggests that pharmacological treatments aimed at H. pylori eradication in the late stages of precursor lesions do not prevent epigenome reprogramming toward a cancer signature.
Note: Reproducció del document publicat a: https://doi.org/10.3390/cancers13112760
It is part of: Cancers, 2021, vol 13
URI: http://hdl.handle.net/2445/178641
Related resource: https://doi.org/10.3390/cancers13112760
Appears in Collections:Articles publicats en revistes (Ciències Fisiològiques)
Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

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