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-1 alpha (HIF-1 alpha), 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-1 alpha, 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.