期刊
INTERNATIONAL JOURNAL OF CANCER
卷 131, 期 6, 页码 1323-1331出版社
WILEY-BLACKWELL
DOI: 10.1002/ijc.27369
关键词
ALU; gastric cancer; hypomethylation; LINE-1; prognosis
类别
资金
- Korea Healthcare Technology R&D Project, Ministry for Health, Welfare & Family Affairs, Republic of Korea [A091081]
- Ministry of Education, Science and Technology (MEST) [M10750030001-08N5003-00110, 2010-0007579]
- Priority Research Centers Program, National Research Foundation of Korea (NRF) [2009-0093820]
- Korea Health Promotion Institute [A091081] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
- National Research Foundation of Korea [2010-0007579] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Focal CpG island hypermethylation and diffuse genomic hypomethylation signify the changes in the DNA methylation status in cancer cells. ALU and LINE-1 repetitive DNA elements comprise similar to 28% of the human genome. PCR-based measurements of these repetitive DNA elements can be used as a surrogate marker of the genomewide methylation content. Our study aimed to identify the timing of ALU and LINE-1 hypomethylations during multistep gastric carcinogenesis and their prognostic implications in gastric cancer (GC). In our study, we analyzed the methylation statuses of ALU and LINE-1 in 249 cases of gastric biopsy samples and another independent set of 198 cases of advanced GC by pyrosequencing. Regardless of the Helicobacter pylori infection status, a significant decrease in the ALU methylation levels was noted during the transitions from chronic gastritis to intestinal metaplasia and from gastric adenoma to GC. LINE-1 methylation decreased during the transition from intestinal metaplasia to gastric adenoma and no further decrease occurred during the transition from gastric adenoma to GC. A low LINE-1 methylation status was strongly associated with poor prognosis in GC. A multivariate analysis revealed that LINE-1 methylation status was an independent prognostic factor. Our findings suggest that ALU and LINE-1 hypomethylations are early events during multistep gastric carcinogenesis. Furthermore, the LINE-1 methylation status can be used as a molecular biomarker to define a subset of GC patients with poor prognosis.
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