title: Single nucleotide polymorphisms associated with metastatic tumour antigen 1 overexpression in patients with hepatocellular carcinoma.
abstract: OBJECTIVE
  Metastatic tumour antigen 1 (MTA1) promotes angiogenesis by stabilizing hypoxia-inducible factor-1α (HIF-1α), which is closely associated with frequent postoperative recurrence and poor survival in patients with HCC. In this study, we determined single nucleotide polymorphisms (SNPs) in angiogenesis-related genes that are associated with MTA1 overexpression in HCC tissues.
  
  
  METHODS
  A total of 376 patients with HCC who had received curative surgical resection or liver transplantation were enrolled (312/21/43; HBV/HCV/NBNC). MTA1 expression was determined via immunohistochemistry. Thirty-three common SNPs sites (frequency ≥5%) in the angiogenic protein gene that are closely connected to one another were selected, including MTA1, VEGF, HIF-1α, FGF-2, and IGF-II.
  
  
  RESULTS
  Expression of MTA1 was detected in 120 HCC tissues (31%). An A allele at position IVS4-81G/A of the MTA1 gene (P = 0.016) and the TT genotype at position +12916C of the VEGF gene (P = 0.023) were significantly associated with MTA1 overexpression. However, the TT genotype at position -13021C (P = 0.011) and the haplotypes CT-CT (-11228C; -13021C) of the IGF-II gene (P(cor) = 0.033) were more common in patients with MTA1-negative HCC. Using multivariate analysis, the A allele at IVS4-81G/A in MTA1 gene (P = 0.015) and a T allele (TT+CT genotype) at -13021C in IGF-II (P = 0.002) were independent risk factors in HCC recurrence after curative surgical resection.
  
  
  CONCLUSIONS
  The genetic polymorphisms IVS4-81G/A in MTA1 and +12916C in VEGF genes were correlated with MTA1 overexpression. The SNPs in MTA1 and IGF-II genes may be important risk factors for the recurrence of HCC.
authors.affiliation: Department of Internal Medicine, Soonchunhyang University College of Medicine, Cheonan, Korea.
authors.forename: Sae Hwan
authors.initials: SH
authors.lastname: Lee
authors.forename: Young-Hwa
authors.initials: YH
authors.lastname: Chung
authors.forename: Jeong A
authors.initials: JA
authors.lastname: Kim
authors.forename: Danbi
authors.initials: D
authors.lastname: Lee
authors.forename: Young-Joo
authors.initials: YJ
authors.lastname: Jin
authors.forename: Ju Hyun
authors.initials: JH
authors.lastname: Shim
authors.forename: Myoung-Kuk
authors.initials: MK
authors.lastname: Jang
authors.forename: Eun-Young
authors.initials: EY
authors.lastname: Cho
authors.forename: Eun-Soon
authors.initials: ES
authors.lastname: Shin
authors.forename: Jong-Eun
authors.initials: JE
authors.lastname: Lee
authors.forename: Neung Hwa
authors.initials: NH
authors.lastname: Park
authors.forename: Eunsil
authors.initials: E
authors.lastname: Yu
authors.forename: Young Joo
authors.initials: YJ
authors.lastname: Lee
mesh_terms: D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000235:genetics*; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006239:Haplotypes / Q000235:genetics; D006655:Histone Deacetylases / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry; D007335:Insulin-Like Growth Factor II / Q000235:genetics / Q000378:metabolism; D008113:Liver Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012008:Recurrence; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism*; D012307:Risk Factors; D015534:Trans-Activators; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C035170:IGF2 protein, human; C089320:MTA1 protein, human; D012097:Repressor Proteins; D015534:Trans-Activators; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D007335:Insulin-Like Growth Factor II; D006655:Histone Deacetylases