Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
, 22 (6), 1109-1120

DNA Methylation Genome-Wide Analysis in Remnant and Primary Gastric Cancers

Affiliations

DNA Methylation Genome-Wide Analysis in Remnant and Primary Gastric Cancers

Kiichi Sugimoto et al. Gastric Cancer.

Abstract

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.

Keywords: DNA methylation; Genome-wide analysis; Helicobacter pylori; Remnant gastric cancer; Tumor suppressor gene.

Similar articles

See all similar articles

References

    1. Cancer Res. 2001 Apr 15;61(8):3225-9 - PubMed

References

    1. N Engl J Med. 2001 Sep 13;345(11):784-9 - PubMed

References

    1. Gastric Cancer. 2015 Apr;18(2):280-7 - PubMed

References

    1. Toxicol Lett. 2003 Apr 11;140-141:99-104 - PubMed

References

    1. Gastric Cancer. 2011 Jun;14(2):101-12 - PubMed

References

    1. Gut. 2018 Feb;67(2):226-236 - PubMed

References

    1. Cancer Res. 2010 Feb 15;70(4):1430-40 - PubMed

References

    1. Br J Surg. 1995 Nov;82(11):1540-3 - PubMed

References

    1. Cancer Cell. 2004 Feb;5(2):121-5 - PubMed

References

    1. Aliment Pharmacol Ther. 1991 Dec;5(6):653-8 - PubMed

References

    1. Gastric Cancer. 2017 Mar;20(Suppl 1):8-15 - PubMed

References

    1. Br J Cancer. 2005 Feb 14;92(3):562-9 - PubMed

References

    1. J Gastroenterol. 2005 Jun;40(6):661-3 - PubMed

References

    1. Gastroenterology. 2012 Sep;143(3):550-563 - PubMed

References

    1. Br J Surg. 2007 Jan;94(1):92-5 - PubMed

References

    1. Cochrane Database Syst Rev. 2016 Mar 31;3:CD011389 - PubMed

References

    1. Lancet. 1986 Nov 22;2(8517):1178-81 - PubMed

References

    1. Br J Surg. 1993 Jan;80(1):54-6 - PubMed

References

    1. J Surg Oncol. 2015 Feb;111(2):208-12 - PubMed

References

    1. Cancer Res. 2011 Dec 1;71(23):7187-97 - PubMed

References

    1. J Exp Med. 1999 Dec 6;190(11):1595-604 - PubMed

References

    1. Nature. 2014 Sep 11;513(7517):202-9 - PubMed

References

    1. Clin Cancer Res. 2017 Apr 15;23(8):1998-2005 - PubMed

References

    1. Am J Pathol. 2002 Mar;160(3):787-94 - PubMed

References

    1. World J Gastroenterol. 2014 Apr 28;20(16):4483-90 - PubMed

References

    1. J Clin Oncol. 2015 Oct 1;33(28):3085-91 - PubMed

References

    1. Gastric Cancer. 2016 Apr;19(2):339-349 - PubMed

References

    1. Gut. 1984 Sep;25(9):975-87 - PubMed

References

    1. J Clin Pathol. 1986 Nov;39(11):1279 - PubMed

References

    1. Gastric Cancer. 2014 Apr;17(2):213-25 - PubMed

References

    1. Cancer Epidemiol Biomarkers Prev. 2011 Jul;20(7):1483-91 - PubMed

References

    1. J Clin Pathol. 1987 Nov;40(11):1387 - PubMed

References

    1. Hum Pathol. 2017 May;63:128-138 - PubMed

References

    1. World J Gastroenterol. 2014 Oct 14;20(38):13734-40 - PubMed

References

    1. Hepatogastroenterology. 2004 Sep-Oct;51(59):1548-50 - PubMed

References

    1. Cancer Res. 2011 Oct 1;71(19):6195-207 - PubMed

References

    1. Am J Surg. 1987 Apr;153(4):399-403 - PubMed

References

    1. Clin Cancer Res. 2006 Feb 1;12(3 Pt 1):989-95 - PubMed

References

    1. J Gastroenterol. 2004 Jun;39(6):520-6 - PubMed

References

    1. CA Cancer J Clin. 2015 Mar;65(2):87-108 - PubMed

References

    1. BMC Res Notes. 2015 Oct 06;8:543 - PubMed

References

    1. Oncol Rep. 2006 Mar;15(3):615-20 - PubMed

References

    1. Gastric Cancer. 2001;4(2):87-92 - PubMed

References

    1. Gynecol Oncol. 2011 Feb;120(2):280-3 - PubMed

References

    1. World J Gastroenterol. 2016 Feb 28;22(8):2424-33 - PubMed

References

    1. N Engl J Med. 2008 Mar 13;358(11):1118-28 - PubMed

References

    1. Helicobacter. 2017 Aug;22(4):null - PubMed

References

    1. J Gastroenterol. 2005 Jun;40(6):563-9 - PubMed

References

    1. Clin Cancer Res. 2012 Feb 15;18(4):923-9 - PubMed

LinkOut - more resources

Feedback