Annals of Surgical Oncology

, Volume 18, Issue 8, pp 2348–2356 | Cite as

Role of MMP14 Gene Polymorphisms in Susceptibility and Pathological Development to Hepatocellular Carcinoma

  • Tzy-Yen Chen
  • Yi-Ching Li
  • Yu-Fan Liu
  • Chiung-Man Tsai
  • Yi-Hsien Hsieh
  • Chiao-Wen Lin
  • Shun-Fa Yang
  • Chia-Jui Weng
Translational Research and Biomarkers

Abstract

Background

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.

Methods

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.

Results

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.

Conclusions

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.

References

  1. 1.
    Itoh Y, Seiki M. MT1-MMP: a potent modifier of pericellular microenvironment. J Cell Physiol. 2006;1:1–8.CrossRefGoogle Scholar
  2. 2.
    Weng CJ, Yen GC. The in vitro and in vivo experimental evidences disclose the chemopreventive effects of Ganoderma lucidum on cancer invasion and metastasis. Clin Exp Metastasis. 2010;27:361–9.PubMedCrossRefGoogle Scholar
  3. 3.
    Ohnishi K, Takagi M, Kurokawa Y, Satomi S, Konttinen YT. Matrix metalloproteinase-mediated extracellular matrix protein degradation in human pulmonary emphysema. Lab Invest. 1998;78:1077–87.PubMedGoogle Scholar
  4. 4.
    Jo Y, Yeon J, Kim HJ, Lee ST. Analysis of tissue inhibitor of metalloproteinases-2 effect on pro-matrix metalloproteinase-2 activation by membrane-type 1 matrix metalloproteinase using baculovirus/insect-cell expression system. Biochem J. 2000;345:511–9.PubMedCrossRefGoogle Scholar
  5. 5.
    Furuya M, Ishikura H, Nemori R, Shibata M, Fujimoto S, Yoshiki T. Clarification of the active gelatinolytic sites in human ovarian neoplasms using in situ zymography. Human Pathol. 2001;32:163–8.CrossRefGoogle Scholar
  6. 6.
    Li Y, Aoki T, Mori Y, Ahmad M, Miyamori H, Takino T, Sato H. Cleavage of lumican by membrane-type matrix metalloproteinase-1 abrogates this proteoglycan-mediated suppression of tumor cell colony formation in soft agar. Cancer Res. 2004;64:7058–64.PubMedCrossRefGoogle Scholar
  7. 7.
    Sabeh F, Ota I, Holmbeck K, et al. Tumor cell traffic through the extracellular matrix is controlled by the membrane-anchored collagenase MT1-MMP. J Cell Biol. 2004;167:769–81.PubMedCrossRefGoogle Scholar
  8. 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
  9. 9.
    Barbolina MV, Adley BP, Ariztia EV, Liu Y, Stack MS. Microenvironmental regulation of membrane type I matrix metalloproteinase activity in ovarian carcinoma cells via collagen-induced EGR1 expression. J Biol Chem. 2007;282:4924–31.PubMedCrossRefGoogle Scholar
  10. 10.
    Hotary KB, Allen ED, Brooks PC, Datta NS, Long MW, Weiss SJ. Membrane type 1 matrix metalloproteinase usurps tumor growth control imposed by the three-dimensional extracellular matrix. Cell. 2003;114:33–45.PubMedCrossRefGoogle Scholar
  11. 11.
    Chen X, Cheung ST, So S, et al. Gene expression patterns in human liver cancers. Mol Biol Cell. 2002;13:1929–39.PubMedCrossRefGoogle Scholar
  12. 12.
    Sood AK, Fletcher MS, Coffin JE, et al. Functional role of matrix metalloproteinases in ovarian tumor cell plasticity. Am J Obstet Gynecol. 2004;190:899–909.PubMedCrossRefGoogle Scholar
  13. 13.
    Davidson B, Goldberg I, Gotlieb WH, Kopolovic J, Ben-Baruch G, Nesland JM, Reich R. The prognostic value of metalloproteinases and angiogenic factors in ovarian carcinoma. Mol Cell Endocrinol. 2002;187:39–45.PubMedCrossRefGoogle Scholar
  14. 14.
    Zhou Z, Apte SS, Soininen R, et al. Impaired endochondral ossification and angiogenesis in mice deficient in membrane-type matrix metalloproteinase I. Proc Natl Acad Sci USA. 2000;97:4052–7.PubMedCrossRefGoogle Scholar
  15. 15.
    Seiki M. Membrane-type 1 matrix metalloproteinase: a key enzyme for tumor invasion. Cancer Lett. 2003;194:1–11.PubMedCrossRefGoogle Scholar
  16. 16.
    Shastry BS. SNP alleles in human disease and evolution. J Hum Genet. 2002;47:561–6.PubMedCrossRefGoogle Scholar
  17. 17.
    Weng CJ, Hsieh YH, Tsai CM, et al. Relationship of insulin-like growth factors system gene polymorphisms with the susceptibility and pathological development of hepatocellular carcinoma. Ann Surg Oncol. 2010;17:1808–15.PubMedCrossRefGoogle Scholar
  18. 18.
    Farazi PA, DePinho RA. Hepatocellular carcinoma pathogenesis: from genes to environment. Nat Rev Cancer. 2006;6:674–87.PubMedCrossRefGoogle Scholar
  19. 19.
    Firpi RJ, Nelson DR. Viral hepatitis: manifestations and management strategy. Hematol Am Soc Hematol Educ Program. 2006;375–80.Google Scholar
  20. 20.
    Yano Y, Yamashita F, Kuwaki K, et al. Clinical features of hepatitis C virus-related hepatocellular carcinoma and their association with alpha-fetoprotein and protein induced by vitamin K absence or antagonist-II. Liver Int. 2006;26:789–95.PubMedCrossRefGoogle Scholar
  21. 21.
    Weng CJ, Tsai CM, Chen YC, et al. Evaluation of the association of urokinase plasminogen activator system gene polymorphisms with susceptibility and pathological development of hepatocellular carcinoma. Ann Surg Oncol. 2010;17:3394–401.PubMedCrossRefGoogle Scholar
  22. 22.
    Feitelson MA. Parallel epigenetic and genetic changes in the pathogenesis of hepatitis virus-associated hepatocellular carcinoma. Cancer Lett. 2006;239:10–20.PubMedCrossRefGoogle Scholar
  23. 23.
    Thorgeirsson SS, Grisham JW. Molecular pathogenesis of human hepatocellular carcinoma. Nat Genet. 2002;31:339–46.PubMedCrossRefGoogle Scholar
  24. 24.
    de Vicente JC, Lequerica-Fernández P, Santamaría J, Fresno MF. Expression of MMP-7 and MT1-MMP in oral squamous cell carcinoma as predictive indicator for tumor invasion and prognosis. J Oral Pathol Med. 2007;36:415–24.PubMedCrossRefGoogle Scholar
  25. 25.
    Chen CJ, Yu MW, Liaw YF. Epidemiological characteristics and risk factors of hepatocellular carcinoma. J Gastroenterol Hepatol. 1997;12:S294–308.PubMedCrossRefGoogle Scholar
  26. 26.
    Chen TH, Chen CJ, Yen MF, et al. Ultrasound screening and risk factors for death from hepatocellular carcinoma in a high-risk group in Taiwan. Int J Cancer. 2002;98:257–61.PubMedCrossRefGoogle Scholar
  27. 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
  28. 28.
    Akkız H, Bayram S, Bekar A, et al. G-308A TNF-alpha polymorphism is associated with an increased risk of hepatocellular carcinoma in the Turkish population: case-control study. Cancer Epidemiol. 2009;33:261–4.PubMedCrossRefGoogle Scholar
  29. 29.
    Chang CC, Chen SC, Hsieh YH, et al. Stromal cell-derived factor-1 but not its receptor, CXCR4, gene variants increase susceptibility and pathological development of hepatocellular carcinoma. Clin Chem Lab Med. 2009;47:412–8.PubMedCrossRefGoogle Scholar
  30. 30.
    Buendia MA. Genetics of hepatocellular carcinoma. Semin Cancer Biol. 2000;10:185-200.PubMedCrossRefGoogle Scholar
  31. 31.
    Ip YC, Cheung ST, Leung KL, Fan ST. Mechanism of metastasis by membrane type 1-matrix metalloproteinase in hepatocellular carcinoma. World J Gastroenterol. 2005;11:6269–76.PubMedGoogle Scholar
  32. 32.
    Ip YC, Cheung ST, Fan ST. A typical localization of membrane type 1-matrix metalloproteinase in the nucleus is associated with aggressive features of hepatocellular carcinoma. Mol Carcinog. 2007;46:225–30.PubMedCrossRefGoogle Scholar
  33. 33.
    Harada T, Arii S, Mise M, et al. Membrane-type matrix metalloproteinase-1 (MT1-MTP) gene is overexpressed in highly invasive hepatocellular carcinomas. J Hepatol. 1998;28:231–9.PubMedCrossRefGoogle Scholar
  34. 34.
    Maatta M, Soini Y, Liakka A, Autio-Harmainen H. Differential expression of matrix metalloproteinase (MMP)-2, MMP-9, and membranetype1-MMP in hepatocellular and pancreatic adenocarcinoma: implications for tumor progression and clinical prognosis. Clin Cancer Res. 2000;6:2726–34.PubMedGoogle Scholar
  35. 35.
    Saitoh W, Sakamoto T, Hegab AE, et al. MMP14 gene polymorphisms in chronic obstructive pulmonary disease. Int J Mol Med. 2006;17:621-6.PubMedGoogle Scholar
  36. 36.
    Miyoshi A, Kitajima Y, Kido S, Shimonishi T, Matsuyama S, Kitahara K, Miyazaki K. Snail accelerates cancer invasion by upregulating MMP expression and is associated with poor prognosis of hepatocellular carcinoma. Br J Cancer. 2005;92:252–8.PubMedGoogle Scholar
  37. 37.
    Golubkov VS, Boyd S, Savinov AY, et al. Membrane type-1 matrix metalloproteinase (MT1-MMP) exhibits an important intracellular cleavage function and causes chromosome instability. J Biol Chem. 2005;280:25079–86.PubMedCrossRefGoogle Scholar
  38. 38.
    Wang BE, Ma WM, Sulaiman A, et al. Demographic, clinical, and virological characteristics of hepatocellular carcinoma in Asia: survey of 414 patients from four countries. J Med Virol. 2002;67:394–400.PubMedCrossRefGoogle Scholar
  39. 39.
    Schwarz KB. Oxidative stress during viral infection: a review. Free Radic Biol Med. 1996;21:641–9.CrossRefGoogle Scholar
  40. 40.
    Mansouri A, Fromenty B, Berson A, et al. Multiple hepatic mitochondrial DNA deletions suggest premature oxidative aging in alcoholic patients. J Hepatol. 1997;27:96–102.PubMedCrossRefGoogle Scholar
  41. 41.
    Merican I, Guan R, Amarapuka D, et al. Chronic hepatitis B virus infection in Asian countries. J Gastroenterol Hepatol 2000;15:1356–61.PubMedCrossRefGoogle Scholar
  42. 42.
    Lavanchy D. Hepatitis B virus epidemiology, disease burden, treatment, and current and emerging prevention and control measures. J Viral Hepat. 2004;11:97–107.CrossRefGoogle Scholar
  43. 43.
    Shifman S, Bronstein M, Sternfeld M, et al. A highly significant association between a COMT haplotype and schizophrenia. Am J Hum Genet. 2002;71:1296–302.PubMedCrossRefGoogle Scholar

Copyright information

© Society of Surgical Oncology 2011

Authors and Affiliations

  • Tzy-Yen Chen
    • 1
    • 2
  • Yi-Ching Li
    • 3
    • 4
  • Yu-Fan Liu
    • 5
  • Chiung-Man Tsai
    • 6
  • Yi-Hsien Hsieh
    • 7
  • Chiao-Wen Lin
    • 7
  • Shun-Fa Yang
    • 4
    • 8
  • Chia-Jui Weng
    • 9
  1. 1.School of MedicineChung Shan Medical UniversityTaichungTaiwan
  2. 2.Department of Internal MedicineChung Shan Medical University HospitalTaichungTaiwan
  3. 3.Department of Pharmacology, School of MedicineChung Shan Medical UniversityTaichungTaiwan
  4. 4.Department of Medical ResearchChung Shan Medical University HospitalTaichungTaiwan
  5. 5.Department of Biomedical SciencesChung Shan Medical UniversityTaichungTaiwan
  6. 6.Chest Hospital, Department of Health, Executive YuanTainanTaiwan
  7. 7.Institute of Biochemistry and BiotechnologyChung Shan Medical UniversityTaichungTaiwan
  8. 8.Institute of MedicineChung Shan Medical UniversityTaichungTaiwan
  9. 9.Graduate Institute of Applied Science of LivingTainan University of TechnologyTainan CityTaiwan

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