Correlations of MMP-2 and TIMP-2 gene polymorphisms with the risk and prognosis of gastric cancer

Int J Clin Exp Med. 2015 Nov 15;8(11):20391-401. eCollection 2015.

Abstract

Aim: To investigate the correlations of MMP-2 and TIMP-2 polymorphisms with the risk and prognosis of gastric cancer (GC).

Methods: With an incorporation of 254 GC patients in the case group and 250 healthy subjects enrolled as the control group, this experiment was conducted. Denaturing high performance liquid chromatography method was adopted to detect all genotypes under partial denaturation, haloptype analysis was completed with the Shesis software. Serum MMP-2 and TIMP-2 levels were determined by the immunohistochemical semi-quantitative analysis. The follow-up examination was conducted after the patients had completed systemic therapy and discharged.

Results: The distribution frequencies of MMP-2-735C/T locus genotypes between groups were compared (P > 0.05). However, the distributions of alleles and genotype frequencies of MMP-2-1306C/T, TIMP-2-303G/A and -418G/C all exhibited statistical difference (all P < 0.05). The gene polymorphism of MMP-2-1306C/T was statistically correlated with the expression of MMP-2 protein (P < 0.05); the same result was also found regarding TIMP-2-303G/A (P < 0.05). The haplotype analysis revealed that the CGC frequency of the case group was apparently higher than that of the control group (P < 0.05), the positive survival rate of CGC was apparently lower than the negative one.

Conclusion: MMP-2-1306C/T, TIMP-2-303G/A and -418G/C variants might be correlated with GC susceptibility. Serum MMP-2 and TIMP-2 protein levels might be associated with GC susceptibility; Additionally, CGC haplotype might be the risk factor of GC.

Keywords: GC; MMP-2; TIMP-2; gene polumorphism; haplotype analysis; immunohistochemistry; prognosis; survival rate.