Role of MMP14 Gene Polymorphisms in Susceptibility and Pathological Development to Hepatocellular Carcinoma
- 299 Downloads
Early detection of hepatocellular carcinoma (HCC) is seldom available because of the lack of reliable markers. Matrix metalloproteinase (MMP) 14 is a cell surface proteinase that displays a broad spectrum of activity against extracellular matrix components and promotes the invasion/metastasis of cells. MMP14 is overexpressed in HCC, and the level is correlated with poor overall survival. The purpose of this study was to examine whether the MMP14 gene polymorphisms are associated with the susceptibility and clinicopathological development of HCC.
A total of 135 patients with HCC and 496 healthy control subjects were recruited. Six single nucleotide polymorphisms (SNPs) of MMP14 genes were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) genotyping and haplotype-base analysis.
A significant (p < 0.05) lower risk for HCC was shown in the individuals with MMP14 +6767 G/A and +7096 C/C genotypes compared with those with corresponding wild-type homozygotes; high frequency for anti-hepatitis C virus and cirrhosis positive were shown in the HCC patients with MMP14 +7096 TC/CC genotype after adjusting for other confounding factors. The distribution frequency of −165 T: +221 T: +6727 C: +6767 G: +7096 T: +8153 G haplotype and diplotype was significantly higher in the HCC patients than healthy control subjects.
The +6767 and +7096 polymorphic genotypes and haplotype −165 T: +221 T: +6727 C: +6767 G: +7096 T: +8153 G of MMP14 gene might contribute to the prediction of susceptibility and pathological development to HCC.
KeywordsHealthy Control Subject MMP14 Gene Polymerase Chain Reaction Restriction Fragment Length Polymorphism Pathological Development Polymorphic Genotype
This study was supported by a research grant from Chung Shan Medical University Hospital, Taiwan (CSH-2011-C-006).
Conflict of interest
No interest conflicts.
- 8.Munshi HG, Wu YI, Mukhopadhyay S, et al. Differential regulation of membrane type 1 matrix metalloproteinase activity by ERK1/2 and p38 MAPK-modulated tissue inhibitor of metalloproteinases 2 expression controls transforming growth factor b1-induced pericellular collagenolysis. J Biol Chem. 2004;279:39042–50.PubMedCrossRefGoogle Scholar
- 19.Firpi RJ, Nelson DR. Viral hepatitis: manifestations and management strategy. Hematol Am Soc Hematol Educ Program. 2006;375–80.Google Scholar
- 27.Tsai MC, Kee KM, Chen YD, Lin LC, Tsai LS, Chen HH, Lu SN. Excess mortality of hepatocellular carcinoma and morbidity of liver cirrhosis and hepatitis in HCV-endemic areas in an HBV-endemic country: geographic variations among 502 villages in southern Taiwan. J Gastroenterol Hepatol. 2007;22:92–8.PubMedCrossRefGoogle Scholar