title: Elevated expression of MDR1 associated with Line-1 hypomethylation in esophageal squamous cell carcinoma.
abstract: BACKGROUND
  The aim is to discuss the relationship of Line-1 methylation and the MDR1 expression in esophageal squamous cell carcinoma (ESCC).
  
  
  METHODS
  We analyzed the methylation level of Line-1 by quantitative real-time MSP, and the expression of MDR1 by real-time RT-PCR in 310 ESCC and corresponding non-tumor tissues.
  
  
  RESULTS
  We found that the methylation index (MI) of Line-1 decreased from 0.90 in non-tumor tissues toward 0.78 in ESCC. The cumulative survival was significantly shorter in ESCC patients with MI ≤ 0.78 (34 months) than that in patients with MI > 0.78 (43 months). There was a statistical difference between MI ≤ 0.78 and MI > 0.78 cases with these clinicopathologic parameters (age, AJCC stage, differentiation; P = 0.010, P < 0.0001, P = 0.015, respectively). These results implied that Line-1 hypomethylation could be more in ESCC patients with older, advanced tumor and poor differentiation group. Meanwhile, ESCC with demethylation of Line-1 were shown elevated MDR1 expression in tumor (Mean-∆∆Ct = 0.21), but ESCC with hypermethylation of Line-1 were considered to be decreased MDR1 expression in tumor (Mean-∆∆Ct = -0.86).
  
  
  CONCLUSIONS
  Line-1 hypomethylation could be as a biomarker of poor prognosis in ESCC patients. MDR1 gene could be activated via epigenetic mechanisms with demethylation of Line-1 in ESCC, and enhance tumor progression.
authors.affiliation: Clinical Oncology Laboratory, Changzhou Cancer Hospital of Soochow University Huaide Road, Changzhou 213002, P. R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Clinical Oncology Laboratory, Changzhou Cancer Hospital of Soochow University Huaide Road, Changzhou 213002, P. R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Ling
authors.affiliation: Department of Oncology, Nanyang Center Hospital Nanyang 473000, Henan, P. R. China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Clinical Oncology Laboratory, Changzhou Cancer Hospital of Soochow University Huaide Road, Changzhou 213002, P. R. China.
authors.forename: Ming-Zhu
authors.initials: MZ
authors.lastname: Lu
authors.affiliation: Clinical Oncology Laboratory, Changzhou Cancer Hospital of Soochow University Huaide Road, Changzhou 213002, P. R. China.
authors.forename: Yong-Ping
authors.initials: YP
authors.lastname: Liu
authors.affiliation: Clinical Oncology Laboratory, Changzhou Cancer Hospital of Soochow University Huaide Road, Changzhou 213002, P. R. China.
authors.forename: Chang-Song
authors.initials: CS
authors.lastname: Zhang
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics / Q000378:metabolism; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology / Q000601:surgery; D002454:Cell Differentiation; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology / Q000601:surgery; D000077277:Esophageal Squamous Cell Carcinoma; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D020084:Long Interspersed Nucleotide Elements; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D016016:Proportional Hazards Models; D060888:Real-Time Polymerase Chain Reaction; D012307:Risk Factors; D015854:Up-Regulation
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D014408:Biomarkers, Tumor
keywords: ESCC; Line-1; MDR1; hypomethylation
references.citation: Ann Surg Oncol. 2011 Aug;18(8):2373-80
references.pmid: 21331808
references.citation: Methods Mol Biol. 2010;596:47-76
references.pmid: 19949920
references.citation: Methods Mol Biol. 2010;596:223-49
references.pmid: 19949927
references.citation: Ann Surg Oncol. 2014 Dec;21 Suppl 4:S696-702
references.pmid: 24898425
references.citation: Drug Resist Updat. 2015 Jan;18:1-17
references.pmid: 25554624
references.citation: Cell Biosci. 2014 Aug 26;4:49
references.pmid: 25922661
references.citation: Cell Tissue Res. 2014 Jun;356(3):643-55
references.pmid: 24816987
references.citation: Ann Surg Oncol. 2012 Aug;19(8):2726-32
references.pmid: 22187122
references.citation: Biochim Biophys Acta. 2007 Jan;1775(1):138-62
references.pmid: 17045745
references.citation: PLoS One. 2014;9(10):e109478
references.pmid: 25275447
references.citation: Ann Surg Oncol. 2012 Dec;19(13):4238-43
references.pmid: 22766991
references.citation: Clin Cancer Res. 2010 Nov 1;16(21):5114-23
references.pmid: 20978145
references.citation: Nat Rev Genet. 2009 Oct;10(10):691-703
references.pmid: 19763152
references.citation: J Clin Pathol. 2011 Mar;64(3):246-51
references.pmid: 21169275
references.citation: Gen Thorac Cardiovasc Surg. 2013 May;61(5):262-9
references.pmid: 23529258
references.citation: Clin Cancer Res. 2014 Mar 1;20(5):1114-24
references.pmid: 24423610
references.citation: Curr Opin Oncol. 2011 Jan;23(1):69-76
references.pmid: 21119515
references.citation: Surg Today. 2013 Dec;43(12):1355-64
references.pmid: 23291904
references.citation: Blood. 2006 Feb 15;107(4):1546-54
references.pmid: 16223781
references.citation: Mol Cell. 2014 Jun 5;54(5):716-27
references.pmid: 24905005
references.citation: Methods Mol Biol. 2010;596:95-121
references.pmid: 19949922
references.citation: Front Med. 2013 Dec;7(4):401-10
references.pmid: 24002746
references.citation: World J Gastrointest Oncol. 2014 May 15;6(5):112-20
references.pmid: 24834141
references.citation: Nat Rev Cancer. 2002 Jan;2(1):48-58
references.pmid: 11902585
references.citation: Lancet. 2013 Feb 2;381(9864):400-12
references.pmid: 23374478
references.citation: Epigenomics. 2009 Dec;1(2):239-59
references.pmid: 20495664
references.citation: Ann Surg. 2013 Mar;257(3):449-55
references.pmid: 23023202
references.citation: J Biol Chem. 2014 Nov 7;289(45):30880-8
references.pmid: 25281745