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Analysis of the clinical significance of DNA methylation in gastric cancer based on a genome-wide high-resolution array

BACKGROUND: Aberrant DNA methylation is involved in gastric carcinogenesis and may serve as a useful biomarker in the diagnosis and detection of gastric cancer (GC) recurrence. RESULTS: A total of 157 patients who received surgery for GC were enrolled in the present study. A genome-wide methylation...

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Autores principales: Fang, Wen-Liang, Chen, Ming-Huang, Huang, Kuo-Hung, Chang, Shih-Ching, Lin, Chien-Hsing, Chao, Yee, Lo, Su-Shun, Li, Anna Fen-Yau, Wu, Chew-Wun, Shyr, Yi-Ming
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6824057/
https://www.ncbi.nlm.nih.gov/pubmed/31675985
http://dx.doi.org/10.1186/s13148-019-0747-5
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author Fang, Wen-Liang
Chen, Ming-Huang
Huang, Kuo-Hung
Chang, Shih-Ching
Lin, Chien-Hsing
Chao, Yee
Lo, Su-Shun
Li, Anna Fen-Yau
Wu, Chew-Wun
Shyr, Yi-Ming
author_facet Fang, Wen-Liang
Chen, Ming-Huang
Huang, Kuo-Hung
Chang, Shih-Ching
Lin, Chien-Hsing
Chao, Yee
Lo, Su-Shun
Li, Anna Fen-Yau
Wu, Chew-Wun
Shyr, Yi-Ming
author_sort Fang, Wen-Liang
collection PubMed
description BACKGROUND: Aberrant DNA methylation is involved in gastric carcinogenesis and may serve as a useful biomarker in the diagnosis and detection of gastric cancer (GC) recurrence. RESULTS: A total of 157 patients who received surgery for GC were enrolled in the present study. A genome-wide methylation analysis was performed in tumor and adjacent normal tissues for the discovery set of 16 GC patients; the top three hypermethylated CpG sites of DNA promoters were selected for validation in tissue and plasma samples for the validation set of 141 GC patients. The frequencies of the top three hypermethylated genes in available patient tissues (n = 141) and plasma samples (n = 106) were 41.8% and 38.7%, respectively, for ADAM19; 40.4% and 42.5%, respectively, for FLI1; and 56.7% and 50.9%, respectively, for MSC. In both tissue and plasma samples, FLI1 hypermethylation was associated with more advanced GC and liver and distant lymphatic metastasis, and ADAM19 hypermethylation was associated with more stage IV GC. In plasma samples, MSC hypermethylation was more common in non-superficial type GC than samples without MSC hypermethylation. In both tissue and plasma samples, patients with methylation of all the three genes had significantly more liver metastases, distant lymphatic metastases, and paraaortic lymph node metastases than patients with two or fewer hypermethylated genes. The survival analysis showed that only for stage III GC, patients with hypermethylation of two or three genes had a worse 5-year disease-free survival rate than those with hypermethylation of one or none of the three genes. Subgroup analysis showed that FLI1 hypermethylation in both tissue and plasma samples was associated with liver metastasis in MSI−/EBV− GC, and MSC hypermethylation in tissue samples was correlated with liver metastasis in MSI+ or EBV+ GC. Patients with FLI1 hypermethylation in plasma samples had a significantly worse 5-year disease-free survival rate than those without FLI1 hypermethylation in MSI−/EBV− GC. FLI1 hypermethylation was an independent prognostic factor affecting the overall survival and disease-free survival in both tissue and plasma samples. CONCLUSIONS: DNA methylation is a useful biomarker for predicting tumor recurrence patterns and GC patient survival.
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spelling pubmed-68240572019-11-06 Analysis of the clinical significance of DNA methylation in gastric cancer based on a genome-wide high-resolution array Fang, Wen-Liang Chen, Ming-Huang Huang, Kuo-Hung Chang, Shih-Ching Lin, Chien-Hsing Chao, Yee Lo, Su-Shun Li, Anna Fen-Yau Wu, Chew-Wun Shyr, Yi-Ming Clin Epigenetics Research BACKGROUND: Aberrant DNA methylation is involved in gastric carcinogenesis and may serve as a useful biomarker in the diagnosis and detection of gastric cancer (GC) recurrence. RESULTS: A total of 157 patients who received surgery for GC were enrolled in the present study. A genome-wide methylation analysis was performed in tumor and adjacent normal tissues for the discovery set of 16 GC patients; the top three hypermethylated CpG sites of DNA promoters were selected for validation in tissue and plasma samples for the validation set of 141 GC patients. The frequencies of the top three hypermethylated genes in available patient tissues (n = 141) and plasma samples (n = 106) were 41.8% and 38.7%, respectively, for ADAM19; 40.4% and 42.5%, respectively, for FLI1; and 56.7% and 50.9%, respectively, for MSC. In both tissue and plasma samples, FLI1 hypermethylation was associated with more advanced GC and liver and distant lymphatic metastasis, and ADAM19 hypermethylation was associated with more stage IV GC. In plasma samples, MSC hypermethylation was more common in non-superficial type GC than samples without MSC hypermethylation. In both tissue and plasma samples, patients with methylation of all the three genes had significantly more liver metastases, distant lymphatic metastases, and paraaortic lymph node metastases than patients with two or fewer hypermethylated genes. The survival analysis showed that only for stage III GC, patients with hypermethylation of two or three genes had a worse 5-year disease-free survival rate than those with hypermethylation of one or none of the three genes. Subgroup analysis showed that FLI1 hypermethylation in both tissue and plasma samples was associated with liver metastasis in MSI−/EBV− GC, and MSC hypermethylation in tissue samples was correlated with liver metastasis in MSI+ or EBV+ GC. Patients with FLI1 hypermethylation in plasma samples had a significantly worse 5-year disease-free survival rate than those without FLI1 hypermethylation in MSI−/EBV− GC. FLI1 hypermethylation was an independent prognostic factor affecting the overall survival and disease-free survival in both tissue and plasma samples. CONCLUSIONS: DNA methylation is a useful biomarker for predicting tumor recurrence patterns and GC patient survival. BioMed Central 2019-11-01 /pmc/articles/PMC6824057/ /pubmed/31675985 http://dx.doi.org/10.1186/s13148-019-0747-5 Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Fang, Wen-Liang
Chen, Ming-Huang
Huang, Kuo-Hung
Chang, Shih-Ching
Lin, Chien-Hsing
Chao, Yee
Lo, Su-Shun
Li, Anna Fen-Yau
Wu, Chew-Wun
Shyr, Yi-Ming
Analysis of the clinical significance of DNA methylation in gastric cancer based on a genome-wide high-resolution array
title Analysis of the clinical significance of DNA methylation in gastric cancer based on a genome-wide high-resolution array
title_full Analysis of the clinical significance of DNA methylation in gastric cancer based on a genome-wide high-resolution array
title_fullStr Analysis of the clinical significance of DNA methylation in gastric cancer based on a genome-wide high-resolution array
title_full_unstemmed Analysis of the clinical significance of DNA methylation in gastric cancer based on a genome-wide high-resolution array
title_short Analysis of the clinical significance of DNA methylation in gastric cancer based on a genome-wide high-resolution array
title_sort analysis of the clinical significance of dna methylation in gastric cancer based on a genome-wide high-resolution array
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6824057/
https://www.ncbi.nlm.nih.gov/pubmed/31675985
http://dx.doi.org/10.1186/s13148-019-0747-5
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