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Single nucleotide polymorphisms associated with metastatic tumour antigen 1 overexpression in patients with hepatocellular carcinoma
Author(s) -
Lee Sae Hwan,
Chung YoungHwa,
Kim Jeong A.,
Lee Danbi,
Jin YoungJoo,
Shim Ju Hyun,
Jang MyoungKuk,
Cho EunYoung,
Shin EunSoon,
Lee JongEun,
Park Neung Hwa,
Yu Eunsil,
Lee Young Joo
Publication year - 2012
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/j.1478-3231.2011.02648.x
Subject(s) - single nucleotide polymorphism , hepatocellular carcinoma , genotype , haplotype , allele , angiogenesis , cancer research , biology , gene , immunohistochemistry , oncology , medicine , pathology , immunology , genetics
Backgrounds/Aims Metastatic tumour antigen 1 ( MTA 1) 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 ( SNP s) in angiogenesis‐related genes that are associated with MTA 1 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 ). MTA 1 expression was determined via immunohistochemistry. Thirty‐three common SNP s sites (frequency ≥5%) in the angiogenic protein gene that are closely connected to one another were selected, including MTA 1, VEGF , HIF ‐1α, FGF ‐2, and IGF ‐ II . Results Expression of MTA 1 was detected in 120 HCC tissues (31%). An A allele at position IVS 4‐81G/A of the MTA 1 gene ( P = 0.016) and the TT genotype at position +12916C of the VEGF gene ( P = 0.023) were significantly associated with MTA 1 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 MTA 1‐negative HCC . Using multivariate analysis, the A allele at IVS 4‐81G/A in MTA 1 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 IVS 4‐81G/A in MTA 1 and +12916C in VEGF genes were correlated with MTA 1 overexpression. The SNP s in MTA 1 and IGF ‐ II genes may be important risk factors for the recurrence of HCC .