Association of MMP-14 gene polymorphisms with the susceptibility and serverity of heptocellular carcinoma

• Main Authors: Hsing-Shan, 洪幸珊
• Other Authors: 謝易修
• Format: Others
• Language: zh-TW
• Published: 2010
• Online Access: http://ndltd.ncl.edu.tw/handle/51276460107218603595

碩士 === 中山醫學大學 === 生化暨生物科技研究所 === 98 === Hepatocellular carcinoma (HCC) is an epithelial cancer that originates from hepatocytes and the most common primary malignant tumor of the liver. The majority of HCC arise in the chronically injured liver as a result of chronic hepatitis and liver cirrhosis. HCC is the fifth most common cancer worldwide and the third most common cause of cancer mortality. At present, the pathogenesis mechanisms of liver cancer are not entirely clear. Long-term prognosis of patients with HCC is generally poor, and survival is mainly affected by the occurrence of metastases. Matrix metalloproteinases (MMPs) are a broad family of zinc-binding endopeptidases that play a key role in the extracellular matrix (ECM) degradation associated with cancer cell invasion, metastasis and angiogenesis. Destruction of the ECM by MMPs has been shown to play an important role in the migration and spreading of tumor cells, leading to invasion and metastasis. Study showed that the MMP-14 gene is strongly expressed in hepatocellular carcinoma cells and is involved in the invasion potential of hepatocellular carcinoma. MMP-14 is a trans- membrane metalloprotease that plays a major role in the extracellular matrix remodeling, directly by degrading several of its components and indirectly by activating pro-MMP2. MMP-14 is indeed a micro- enviroment modifier and also a cell function modifier. Recently, functional gene polymorphisms in MMPs have been found, and some reports have revealed an association between these polymorphisms and the susceptibility of various cancers. The aim of the present study was to investigate the association of MMP-14 gene polymorphisms (-165 G/T, +7096 T/C and +8153 G/A) with the susceptibility and serverity of heptocellular carcinoma. A total of 102 patients with HCC cases were obtained from Chung Shan Medical University Hospital. Of which 347 control subjects were selected from people who came for routine physical checkups. Polymorphism of sites within the promoter region and exon of MMP-14 gene were analyzed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique on genomic DNA extracted from whole blood. Statistical analysis were conducted to explore the differences in the distribution of alleles and genotypes between patients and controls. But also analysis of MMP-14 gene polymorphisms and clinical features of liver cancer, including clinical stage, tumor size, lymph node metastasis, distant metastasis, Child-Pugh grade, HBsAg, AntiHCV and cirrhosis. Result indicated that there was a significant difference in the distribution frequency of MMP-14 +7096 polymorphism between case and control group (p = 0.019), carry T allele increased the susceptibility to HCC than carry C allele (p = 0.005). In HCC clinical features, individuals with -165 G/G genotype had a poor liver synthetic capacity as compared to those with G/T or T/T genotype in the HCC patient group (p = 0.005). These results have demonstrated a significant association between the polymorphisms of MMP-14 gene with the susceptibility and serverity of HCC in the Taiwanese population.