title: Ndrg2 promoter hypermethylation triggered by helicobacter pylori infection correlates with poor patients survival in human gastric carcinoma.
abstract: N-myc downstream regulated gene 2 (Ndrg2) is a candidate suppressor of cancer metastasis. We found that Ndrg2 promoter was frequently hypermethylated in gastric cancer cell lines and in 292 gastric tumor tissues. This resulted in down-regulation of Ndrg2 mRNA and protein. Ndrg2 promoter methylation was associated with H. pylori infection and worse prognosis of gastric cancer patients, which is an independent prognostic factor for the disease-free survival (DFS). We found that H. pylori silenced Ndrg2 by activating the NF-κB pathway and up-regulating DNMT3b, promoting gastric cancer progression. These findings uncover a previously unrecognized role for H. pylori infection in gastric cancer.
authors.affiliation: Zhejiang Cancer Research Institute, Zhejiang Province Cancer Hospital, Zhejiang Cancer Center, Hangzhou, China.
authors.forename: Zhi-Qiang
authors.initials: ZQ
authors.lastname: Ling
authors.affiliation: Department of Tumor Surgery, Zhejiang Province Cancer Hospital, Zhejiang Cancer Center, Hangzhou, China.
authors.forename: Ming-Hua
authors.initials: MH
authors.lastname: Ge
authors.affiliation: Zhejiang Cancer Research Institute, Zhejiang Province Cancer Hospital, Zhejiang Cancer Center, Hangzhou, China.
authors.forename: Xiao-Xiao
authors.initials: XX
authors.lastname: Lu
authors.affiliation: Zhejiang Cancer Research Institute, Zhejiang Province Cancer Hospital, Zhejiang Cancer Center, Hangzhou, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Han
authors.affiliation: Zhejiang Cancer Research Institute, Zhejiang Province Cancer Hospital, Zhejiang Cancer Center, Hangzhou, China.
authors.forename: Yi-Chen
authors.initials: YC
authors.lastname: Wu
authors.affiliation: Zhejiang Cancer Research Institute, Zhejiang Province Cancer Hospital, Zhejiang Cancer Center, Hangzhou, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Liu
authors.affiliation: Zhejiang Cancer Research Institute, Zhejiang Province Cancer Hospital, Zhejiang Cancer Center, Hangzhou, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Zhejiang Cancer Research Institute, Zhejiang Province Cancer Hospital, Zhejiang Cancer Center, Hangzhou, China.
authors.forename: Lian-Lian
authors.initials: LL
authors.lastname: Hong
mesh_terms: D045744:Cell Line, Tumor; D019175:DNA Methylation; D016481:Helicobacter Infections / Q000235:genetics* / Q000378:metabolism; D016480:Helicobacter pylori / Q000378:metabolism*; D006801:Humans; D011401:Promoter Regions, Genetic; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000382:microbiology*; D016019:Survival Analysis; D014162:Transfection; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: C466228:NDRG2 protein, human; D025521:Tumor Suppressor Proteins
keywords: DNMT3b; Helicobacter pylori (H. pylori) infection; N-myc downstream regulated gene 2 (Ndrg2); gastric carcinoma; promoter methylation
references.citation: Am J Pathol. 2007 Nov;171(5):1520-8
references.pmid: 17982128
references.citation: BMJ. 1991 Jun 1;302(6788):1302-5
references.pmid: 2059685
references.citation: Cancer Res. 2010 Feb 15;70(4):1430-40
references.pmid: 20124475
references.citation: Epigenetics. 2012 Jul;7(7):701-9
references.pmid: 22647880
references.citation: J Biomed Biotechnol. 2012;2012:623019
references.pmid: 22363173
references.citation: Gut. 2009 Jan;58(1):5-15
references.pmid: 18664505
references.citation: Biochem Biophys Res Commun. 2011 Mar 25;406(4):534-8
references.pmid: 21352815
references.citation: J Immunol. 2014 Oct 1;193(7):3566-76
references.pmid: 25172489
references.citation: Oncotarget. 2014 Nov 30;5(22):11631-40
references.pmid: 25373785
references.citation: Dig Dis Sci. 2013 Mar;58(3):715-23
references.pmid: 23010743
references.citation: Carcinogenesis. 2008 Jan;29(1):2-8
references.pmid: 17916902
references.citation: Nat Rev Genet. 2002 Jun;3(6):415-28
references.pmid: 12042769
references.citation: Biochem Biophys Res Commun. 2007 Jun 22;358(1):164-9
references.pmid: 17470364
references.citation: J Neurooncol. 2013 Jul;113(3):441-9
references.pmid: 23624749
references.citation: Gastroenterology. 1998 Sep;115(3):642-8
references.pmid: 9721161
references.citation: Mol Cancer. 2008;7:15
references.pmid: 18221536
references.citation: Genomics. 2001 Apr 1;73(1):86-97
references.pmid: 11352569
references.citation: Mech Dev. 1999 May;83(1-2):39-52
references.pmid: 10381566
references.citation: Dig Dis Sci. 2010 Apr;55(4):1011-6
references.pmid: 19517237
references.citation: Carcinogenesis. 2007 Dec;28(12):2434-42
references.pmid: 17893234
references.citation: Gastric Cancer. 2013 Oct;16(4):488-97
references.pmid: 23292007
references.citation: Exp Mol Med. 2007 Dec 31;39(6):705-14
references.pmid: 18160841
references.citation: Oncotarget. 2015 Jan 30;6(3):1531-43
references.pmid: 25605238
references.citation: Mol Cell Biochem. 2002 Jan;229(1-2):35-44
references.pmid: 11936845
references.citation: Eur J Biochem. 2002 Oct;269(20):4981-4
references.pmid: 12383256
references.citation: Gastroenterology. 2010 Dec;139(6):2005-17
references.pmid: 20801119
references.citation: Helicobacter. 2010 Sep;15 Suppl 1:34-9
references.pmid: 21054651
references.citation: Curr Mol Med. 2007 Feb;7(1):15-28
references.pmid: 17311530
references.citation: PLoS One. 2013 Jun 27;8(6):e67195
references.pmid: 23826230
references.citation: J Clin Endocrinol Metab. 2013 Jan;98(1):E174-84
references.pmid: 23093492
references.citation: Int J Cancer. 2008 Nov 1;123(9):2080-6
references.pmid: 18709645
references.citation: World J Gastroenterol. 2014 Apr 14;20(14):3916-26
references.pmid: 24744581
references.citation: Oncotarget. 2014 Jul 30;5(14):5798-807
references.pmid: 25015565
references.citation: Cancer Res. 2008 Jun 1;68(11):4210-20
references.pmid: 18519680
references.citation: Biochem Biophys Res Commun. 2010 Jan 22;391(4):1785-91
references.pmid: 20045673
references.citation: Cancer Res. 2006 Jan 15;66(2):682-92
references.pmid: 16423997
references.citation: BMC Med Genomics. 2009 Mar 03;2:11
references.pmid: 19257893
references.citation: Cancer Lett. 2010 Nov 28;297(2):244-51
references.pmid: 20831982
references.citation: Folia Histochem Cytobiol. 2006;44(3):143-54
references.pmid: 16977793
references.citation: Biochem Biophys Res Commun. 2013 Nov 8;441(1):102-7
references.pmid: 24134849
references.citation: Ann Surg Oncol. 2012 Aug;19(8):2763-72
references.pmid: 22246425
references.citation: N Engl J Med. 2002 Oct 10;347(15):1175-86
references.pmid: 12374879
references.citation: Clin Cancer Res. 2003 Oct 1;9(12):4415-22
references.pmid: 14555514
references.citation: IARC Monogr Eval Carcinog Risks Hum. 1994;61:177-240
references.pmid: 7715070
references.citation: Oncotarget. 2012 Oct;3(10):1057-8
references.pmid: 23165367
references.citation: Methods Enzymol. 2009;463:73-95
references.pmid: 19892168
references.citation: Gastroenterology. 2013 Jan;144(1):122-133.e9
references.pmid: 23058321
references.citation: Clin Chim Acta. 2013 Sep 23;424:53-65
references.pmid: 23669186
references.citation: J Gastrointest Oncol. 2012 Sep;3(3):251-61
references.pmid: 22943016
references.citation: Hum Mol Genet. 2000 Oct;9(16):2395-402
references.pmid: 11005794
references.citation: N Engl J Med. 1991 Oct 17;325(16):1127-31
references.pmid: 1891020
references.citation: Cancer. 2012 Nov 15;118(22):5507-17
references.pmid: 22576578
references.citation: J Pathol. 2004 Sep;204(1):75-83
references.pmid: 15307140
references.citation: Cancer Res. 2005 Aug 15;65(16):7121-6
references.pmid: 16103061
references.citation: Gastroenterology. 2011 Mar;140(3):879-91
references.pmid: 21111741
references.citation: Biochim Biophys Acta. 2001 May 28;1519(1-2):134-8
references.pmid: 11406283
references.citation: PLoS One. 2014;9(6):e98899
references.pmid: 24901306
references.citation: Acta Biochim Biophys Sin (Shanghai). 2008 Jul;40(7):625-35
references.pmid: 18604454
references.citation: Oncol Rep. 2010 Mar;23(3):819-26
references.pmid: 20127025