Cargando…
Follow-Up Study Confirms the Presence of Gastric Cancer DNA Methylation Hallmarks in High-Risk Precursor Lesions
SIMPLE SUMMARY: 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 progress...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8199626/ https://www.ncbi.nlm.nih.gov/pubmed/34199386 http://dx.doi.org/10.3390/cancers13112760 |
_version_ | 1783707420681306112 |
---|---|
author | Gómez, Antonio Pato, Miguel L. Bujanda, Luis Sala, Núria Companioni, Osmel Cosme, Ángel Tufano, Martina Hanly, David J. García, Nadia Sanz-Anquela, José Miguel Gisbert, Javier P. López, Consuelo Elizalde, José Ignacio Cuatrecasas, 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 |
author_facet | Gómez, Antonio Pato, Miguel L. Bujanda, Luis Sala, Núria Companioni, Osmel Cosme, Ángel Tufano, Martina Hanly, David J. García, Nadia Sanz-Anquela, José Miguel Gisbert, Javier P. López, Consuelo Elizalde, José Ignacio Cuatrecasas, 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 |
author_sort | Gómez, Antonio |
collection | PubMed |
description | SIMPLE SUMMARY: 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. ABSTRACT: 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. |
format | Online Article Text |
id | pubmed-8199626 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-81996262021-06-14 Follow-Up Study Confirms the Presence of Gastric Cancer DNA Methylation Hallmarks in High-Risk Precursor Lesions Gómez, Antonio Pato, Miguel L. Bujanda, Luis Sala, Núria Companioni, Osmel Cosme, Ángel Tufano, Martina Hanly, David J. García, Nadia Sanz-Anquela, José Miguel Gisbert, Javier P. López, Consuelo Elizalde, José Ignacio Cuatrecasas, 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 Cancers (Basel) Article SIMPLE SUMMARY: 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. ABSTRACT: 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. MDPI 2021-06-02 /pmc/articles/PMC8199626/ /pubmed/34199386 http://dx.doi.org/10.3390/cancers13112760 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Gómez, Antonio Pato, Miguel L. Bujanda, Luis Sala, Núria Companioni, Osmel Cosme, Ángel Tufano, Martina Hanly, David J. García, Nadia Sanz-Anquela, José Miguel Gisbert, Javier P. López, Consuelo Elizalde, José Ignacio Cuatrecasas, 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 Follow-Up Study Confirms the Presence of Gastric Cancer DNA Methylation Hallmarks in High-Risk Precursor Lesions |
title | Follow-Up Study Confirms the Presence of Gastric Cancer DNA Methylation Hallmarks in High-Risk Precursor Lesions |
title_full | Follow-Up Study Confirms the Presence of Gastric Cancer DNA Methylation Hallmarks in High-Risk Precursor Lesions |
title_fullStr | Follow-Up Study Confirms the Presence of Gastric Cancer DNA Methylation Hallmarks in High-Risk Precursor Lesions |
title_full_unstemmed | Follow-Up Study Confirms the Presence of Gastric Cancer DNA Methylation Hallmarks in High-Risk Precursor Lesions |
title_short | Follow-Up Study Confirms the Presence of Gastric Cancer DNA Methylation Hallmarks in High-Risk Precursor Lesions |
title_sort | follow-up study confirms the presence of gastric cancer dna methylation hallmarks in high-risk precursor lesions |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8199626/ https://www.ncbi.nlm.nih.gov/pubmed/34199386 http://dx.doi.org/10.3390/cancers13112760 |
work_keys_str_mv | AT gomezantonio followupstudyconfirmsthepresenceofgastriccancerdnamethylationhallmarksinhighriskprecursorlesions AT patomiguell followupstudyconfirmsthepresenceofgastriccancerdnamethylationhallmarksinhighriskprecursorlesions AT bujandaluis followupstudyconfirmsthepresenceofgastriccancerdnamethylationhallmarksinhighriskprecursorlesions AT salanuria followupstudyconfirmsthepresenceofgastriccancerdnamethylationhallmarksinhighriskprecursorlesions AT companioniosmel followupstudyconfirmsthepresenceofgastriccancerdnamethylationhallmarksinhighriskprecursorlesions AT cosmeangel followupstudyconfirmsthepresenceofgastriccancerdnamethylationhallmarksinhighriskprecursorlesions AT tufanomartina followupstudyconfirmsthepresenceofgastriccancerdnamethylationhallmarksinhighriskprecursorlesions AT hanlydavidj followupstudyconfirmsthepresenceofgastriccancerdnamethylationhallmarksinhighriskprecursorlesions AT garcianadia followupstudyconfirmsthepresenceofgastriccancerdnamethylationhallmarksinhighriskprecursorlesions AT sanzanquelajosemiguel followupstudyconfirmsthepresenceofgastriccancerdnamethylationhallmarksinhighriskprecursorlesions AT gisbertjavierp followupstudyconfirmsthepresenceofgastriccancerdnamethylationhallmarksinhighriskprecursorlesions AT lopezconsuelo followupstudyconfirmsthepresenceofgastriccancerdnamethylationhallmarksinhighriskprecursorlesions AT elizaldejoseignacio followupstudyconfirmsthepresenceofgastriccancerdnamethylationhallmarksinhighriskprecursorlesions AT cuatrecasasmiriam followupstudyconfirmsthepresenceofgastriccancerdnamethylationhallmarksinhighriskprecursorlesions AT andreuvictoria followupstudyconfirmsthepresenceofgastriccancerdnamethylationhallmarksinhighriskprecursorlesions AT paulesmariajose followupstudyconfirmsthepresenceofgastriccancerdnamethylationhallmarksinhighriskprecursorlesions AT martinarranzmariadolores followupstudyconfirmsthepresenceofgastriccancerdnamethylationhallmarksinhighriskprecursorlesions AT ortegaluis followupstudyconfirmsthepresenceofgastriccancerdnamethylationhallmarksinhighriskprecursorlesions AT poveselvira followupstudyconfirmsthepresenceofgastriccancerdnamethylationhallmarksinhighriskprecursorlesions AT barriojesus followupstudyconfirmsthepresenceofgastriccancerdnamethylationhallmarksinhighriskprecursorlesions AT torresmariaangeles followupstudyconfirmsthepresenceofgastriccancerdnamethylationhallmarksinhighriskprecursorlesions AT munozguillermo followupstudyconfirmsthepresenceofgastriccancerdnamethylationhallmarksinhighriskprecursorlesions AT ferrandezangel followupstudyconfirmsthepresenceofgastriccancerdnamethylationhallmarksinhighriskprecursorlesions AT ramirezlazaromariajose followupstudyconfirmsthepresenceofgastriccancerdnamethylationhallmarksinhighriskprecursorlesions AT lariosergio followupstudyconfirmsthepresenceofgastriccancerdnamethylationhallmarksinhighriskprecursorlesions AT gonzalezcarlosa followupstudyconfirmsthepresenceofgastriccancerdnamethylationhallmarksinhighriskprecursorlesions AT estellermanel followupstudyconfirmsthepresenceofgastriccancerdnamethylationhallmarksinhighriskprecursorlesions AT berdascomaria followupstudyconfirmsthepresenceofgastriccancerdnamethylationhallmarksinhighriskprecursorlesions |