Single nucleotide polymorphisms associated with metastatic tumour antigen 1 overexpression in patients with hepatocellular carcinoma
- Abstract
- Backgrounds/aims: 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.
- All Author(s)
- S. H. Lee
; Y. H. Chung
; J. A. Kim
; D. Lee
; Y. J. Jin
; J. H. Shim
; M. K. Jang
; E. Y. Cho
; E. S. Shin
; J. E. Lee
; N. H. Park
; E. Yu
; Y. J. Lee
- Issued Date
- 2012
- Type
- Article
- Keyword
- angiogenesis; hepatocellular carcinoma; MTA1; polymorphism
- Publisher
- International Association for the Study of the Liver
- ISSN
- 1478-3223
; 1478-3231
- Citation Title
- Liver international
- Citation Volume
- 32
- Citation Number
- 3
- Citation Start Page
- 457
- Citation End Page
- 466
- Language(ISO)
- eng
- DOI
- 10.1111/j.1478-3231.2011.02648.x
- URI
- http://schca-ir.schmc.ac.kr/handle/2022.oak/2385
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