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Although gastric cancer (GC) in young adults (= 45 years) accounts for fewer than 10% of newly diagnosed cases, the young patients are more likely to have advanced disease at presentation compared with elderly patients. Previous studies have identified that the DNA methylation of genomes are different during aging. Our study aimed to explore the association between DNA methylation and the onset of GC. We applied Illumina HumanMethylation450 BeadChip to examine methylation expression profiles and compared methylation expression patterns in five early onset GC patients and seven elderly patients. Additionally, we evaluated the associations of methylation expression with different clinicopathological characteristics of GC. Our results showed that the pattern of genome-wide methylation expression was significantly different between early onset and elderly GC. The top 10 hypomethylation and hypermethylation CpG sites were selected for further analyses in The Cancer Genome Atlas (TCGA) database. We found that the hypermethylation of cg11037477, located at the promoter of EIF4E, was significantly associated with age at diagnosis and the expression of EIF4E. Besides, GC patients with high level of cg11037477 were more likely to have advance disease with T3/T4 invasion and III/IV stage. The cg11037477 hypermethylation and EIF4E down-expression were significantly related to poor survival of GC patients. Our study provides new insights into the molecular mechanism of early onset patients with GC and suggests that methylation of cg11037477 and expression of EIF4E may act as prognostic markers in GC. [ABSTRACT FROM AUTHOR]