title: Aberrant methylation of the PTPRO gene in peripheral blood as a potential biomarker in esophageal squamous cell carcinoma patients.
abstract: Epigenetic inactivation of protein tyrosine phosphatase receptor-type O (PTPRO), a new member of the PTP family, has been described in several forms of cancer. We evaluated PTPRO promoter hypermethylation as a potential biomarker in esophageal squamous cell carcinoma (ESCC). This alteration was observed in 27 (75%) of 36 primary tumors and correlated significantly with depth of invasion (T-stage, P = 0.013). Among matched peripheral blood samples from ESCC patients, 13 (36.1%) of 36 exhibited detectable methylated PTPRO in plasma, while 15 (41.7%) of 36 had this abnormality in buffy coat. No methylated PTPRO was observed in normal peripheral blood samples from 10 healthy individuals. In addition, demethylation by 5-aza-dC treatment led to gene reactivation in PTPRO-methylated and -silenced ESCC cell lines. To our knowledge, this is the first report of methylated PTPRO as a noninvasive tumor biomarker in peripheral blood. These findings suggest that hypermethylated PTPRO occurs frequently in ESCC. Further, detection in peripheral blood of ESCC patients suggests potential clinical application for noninvasive diagnosis and disease monitoring.
authors.affiliation: Department of Integrative Chinese and Western Medicine, Cancer Hospital of Shantou University Medical College, Shantou, People's Republic of China.
authors.forename: Yan-Jie
authors.initials: YJ
authors.lastname: You
authors.forename: Yu-Ping
authors.initials: YP
authors.lastname: Chen
authors.forename: Xiao-Xuan
authors.initials: XX
authors.lastname: Zheng
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Meltzer
authors.forename: Hao
authors.initials: H
authors.lastname: Zhang
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood*; D002294:Carcinoma, Squamous Cell / Q000201:enzymology / Q000235:genetics* / Q000503:physiopathology*; D045744:Cell Line, Tumor; D004938:Esophageal Neoplasms / Q000097:blood / Q000201:enzymology / Q000235:genetics* / Q000503:physiopathology*; D005260:Female; D006801:Humans; D008297:Male; D008745:Methylation; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3 / Q000097:blood / Q000235:genetics / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3
references.citation: Cancer Gene Ther. 2005 Aug;12(8):665-72
references.pmid: 15803146
references.citation: J Biol Chem. 2009 Jan 2;284(1):455-464
references.pmid: 18997174
references.citation: Semin Radiat Oncol. 2007 Jan;17(1):2-9
references.pmid: 17185192
references.citation: Eur J Med Res. 2010;15:277-86
references.pmid: 20696638
references.citation: Transfusion. 2001 Feb;41(2):276-82
references.pmid: 11239235
references.citation: FEBS Lett. 2008 Aug 20;582(19):2850-6
references.pmid: 18644370
references.citation: Oncogene. 2003 Sep 25;22(41):6319-31
references.pmid: 14508512
references.citation: Cancer Res. 2002 Jan 15;62(2):371-5
references.pmid: 11809682
references.citation: Cancer Genet Cytogenet. 2002 Jun;135(2):120-7
references.pmid: 12127396
references.citation: FEBS Lett. 2010 Sep 24;584(18):3923-8
references.pmid: 20804755
references.citation: Clin Cancer Res. 2003 Aug 1;9(8):3042-6
references.pmid: 12912954
references.citation: J Natl Cancer Inst. 1999 Feb 17;91(4):332-9
references.pmid: 10050866
references.citation: Cancer Res. 2001 Feb 1;61(3):939-42
references.pmid: 11221887
references.citation: Nat Rev Genet. 2005 Aug;6(8):597-610
references.pmid: 16136652
references.citation: Oral Oncol. 2007 Jan;43(1):82-7
references.pmid: 16807071
references.citation: Int J Cancer. 2008 Nov 15;123(10):2331-6
references.pmid: 18729198
references.citation: Clin Cancer Res. 2007 Jun 1;13(11):3174-81
references.pmid: 17545520
references.citation: Adv Enzyme Regul. 1999;39:359-69
references.pmid: 10470384
references.citation: Cancer Res. 2001 Mar 15;61(6):2727-31
references.pmid: 11289154
references.citation: Mol Endocrinol. 2009 Feb;23(2):176-87
references.pmid: 19095770
references.citation: Cancer Lett. 2010 Jul 1;293(1):41-51
references.pmid: 20092939
references.citation: Cancer Res. 2001 Feb 15;61(4):1659-65
references.pmid: 11245480
references.citation: Cancer Epidemiol Biomarkers Prev. 2008 Jan;17(1):111-7
references.pmid: 18199717
references.citation: CA Cancer J Clin. 2005 Mar-Apr;55(2):74-108
references.pmid: 15761078
references.citation: J Biol Chem. 1994 Aug 5;269(31):19953-62
references.pmid: 7519601
references.citation: J Cancer Res Clin Oncol. 2009 Sep;135(9):1231-7
references.pmid: 19259700
references.citation: Clin Cancer Res. 2007 Nov 1;13(21):6293-300
references.pmid: 17975140
references.citation: Proc Natl Acad Sci U S A. 2004 Sep 21;101(38):13844-9
references.pmid: 15356345
references.citation: Nutr Cancer. 2010;62(4):543-53
references.pmid: 20432176
references.citation: Clin Cancer Res. 2001 Sep;7(9):2727-30
references.pmid: 11555585
references.citation: Blood. 1999 Oct 1;94(7):2403-13
references.pmid: 10498613
references.citation: Cancer Epidemiol Biomarkers Prev. 2007 Jun;16(6):1178-84
references.pmid: 17548682
references.citation: Clin Cancer Res. 2003 Mar;9(3):1047-52
references.pmid: 12631605