DNA methylation genome-wide analysis in remnant and primary gastric cancers

• Published in: Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association Vol. 22; no. 6; pp. 1109 - 1120
• Main Authors: Sugimoto, Kiichi, Ito, Tomoaki, Hulbert, Alicia, Chen, Chen, Orita, Hajime, Maeda, Masahiro, Moro, Hiroshi, Fukagawa, Takeo, Ushijima, Toshikazu, Katai, Hitoshi, Wada, Ryo, Sato, Koichi, Sakamoto, Kazuhiro, Yu, Wayne, Considine, Michael, Cope, Leslie, Brock, Malcolm V.
• Format: Journal Article
• Language: English
• Published: Singapore Springer Singapore 01.11.2019; Springer Nature B.V
• Subjects: Abdominal Surgery; Aged; Aged, 80 and over; Cancer Research; Carcinogenesis; Deoxyribonucleic acid; DNA; DNA Methylation; DNA microarrays; Female; Gastric cancer; Gastric Stump - pathology; Gastroenterology; Genome-Wide Association Study; Genomes; Helicobacter Infections - epidemiology; Helicobacter pylori - isolation & purification; Humans; Male; Medicine; Medicine & Public Health; Middle Aged; Multivariate analysis; Oligonucleotide Array Sequence Analysis; Oncology; Original Article; Promoter Regions, Genetic; Retinal ganglion cells; Stomach Neoplasms - genetics; Stomach Neoplasms - pathology; Surgical Oncology; DNA methylation; Remnant gastric cancer; Genome-wide analysis; Tumor suppressor gene; Helicobacter pylori
• ISSN: 1436-3291; 1436-3305
• DOI: 10.1007/s10120-019-00949-5

Background Although primary (PGC) and remnant gastric cancers (RGC) both originate from the same gastrointestinal organ, they have very distinct clinicopathological behaviors. We hypothesized that there would be distinct differences in DNA methylation patterns that would occur during carcinogenesis of RGC and PGC, and that the differences in methylation patterns may help identify the primary factor contributing to chronic inflammation in patients with RGC. Methods We investigated the genome-wide DNA methylation patterns of PGC and RGC tissues from 48 patients using the Infinium HumanMethylation450 Beadchip assay. The results were validated by quantitative methylation-specific PCR (qMSP) in separate, independent cohorts. Results We found that in our training cohort of 48 patients, the most variable genes from the gastric cancer tissues identified by the Infinium HumanMethylation450 Beadchip clustered the resultant heatmap into high and low methylation groups. On multivariate analysis, PGCs contributed significantly to the high methylation group ( p  = 0.004, OR 12.33), which suggested that the promoter methylation status in PGC is higher than that in RGC. Supporting this conclusion was the finding that in a separate qMSP analysis in a test cohort, the EPB41L3 gene, chosen because of its high β value on microarray analysis in the gastric cancer tissues, had significantly higher DNA promoter methylation in cancer tissues in the validation PGC tissues than in RGC. Conclusions This study demonstrated that promoter methylation status in PGC is higher than in RGC. This result may reflect the effects of the absence of Helicobacter pylori on the reduced DNA methylation in the remnant stomach.