Skip to main content

Advertisement

SpringerLink
Log in

The prognostic role of matrix metalloproteinase 2 in gastric cancer: a systematic review with meta-analysis

  • Original Article - Clinical Oncology
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Abstract

Purpose

The prognostic role of matrix metalloproteinase 2 (MMP-2) in gastric cancer remains controversial. We systematically reviewed the evidence for assessment of MMP-2 expression in gastric cancer to elucidate this issue.

Method

Pubmed, Embase and Web of Science were searched to identify eligible studies to evaluate the association of MMP-2 expression and overall survival and clinicopathological features of gastric cancer.

Results

MMP-2 overexpression was significantly correlated with poor OS of gastric cancer patients (HR 1.92, 95 % CI 1.48–2.48). Subgroup analysis indicated that MMP-2 overexpression had an unfavorable impact on OS in Asian countries (HR 2.23, 95 % CI 1.57–3.17) and European countries (HR 1.43, 95 % CI 1.13–1.80). Furthermore, MMP-2 overexpression was significantly associated with TNM stage (TIII/TIV vs TI/TII: OR 2.17, 95 % CI 1.64–2.87), the depth of invasion (T3/T4 vs T1/T2: OR 2.59, 95 % CI 1.63–4.12), lymph node metastasis (positive vs negative: OR 2.21, 95 % CI 1.69–2.88), and distant metastasis (positive vs negative: OR 4.44, 95 % CI 1.24–15.94).

Conclusion

This meta-analysis indicated that MMP-2 overexpression might be a predictive factor for poor prognosis for gastric cancer.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Abbreviations

MMP-2:

Matrix metalloproteinase 2

HR:

Hazard ratio

OR:

Odds ratio

OS:

Overall survival

References

  • Alakus H, Grass G, Hennecken JK, Bollschweiler E, Schulte C, Drebber U, Baldus SE, Metzger R, Holscher AH, Monig SP (2008) Clinicopathological significance of MMP-2 and its specific inhibitor TIMP-2 in gastric cancer. Histol Histopathol 23(8):917–923

    CAS  PubMed  Google Scholar 

  • Allgayer H, Babic R, Beyer BC, Grutzner KU, Tarabichi A, Schildberg FW, Heiss MM (1998) Prognostic relevance of MMP-2 (72-kD collagenase IV) in gastric cancer. Oncology 55(2):152–160

    Article  CAS  PubMed  Google Scholar 

  • Chen Y, Huang Y, Huang Y, Xia X, Zhang J, Zhou Y, Tan Y, He S, Qiang F, Li A, Re OD, Li G, Zhou J (2013) JWA suppresses tumor angiogenesis via Sp1-activated matrix metalloproteinase-2 and its prognostic significance in human gastric cancer. Carcinogenesis. doi:10.1093/carcin/bgt311

    Google Scholar 

  • Dalberg K, Eriksson E, Enberg U, Kjellman M, Backdahl M (2000) Gelatinase A, membrane type 1 matrix metalloproteinase, and extracellular matrix metalloproteinase inducer mRNA expression: correlation with invasive growth of breast cancer. World J Surg 24(3):334–340

    Article  CAS  PubMed  Google Scholar 

  • Deveci MS, Deveci G (2007) Prognostic value of p53 protein and MK-1 (a tumor-associated antigen) expression in gastric carcinoma. Gastric Cancer 10(2):112–116. doi:10.1007/s10120-007-0418-7

    Article  CAS  PubMed  Google Scholar 

  • Dicken BJ, Graham K, Hamilton SM, Andrews S, Lai R, Listgarten J, Jhangri GS, Saunders LD, Damaraju S, Cass C (2006) Lymphovascular invasion is associated with poor survival in gastric cancer: an application of gene-expression and tissue array techniques. Ann Surg 243(1):64–73

    Article  PubMed Central  PubMed  Google Scholar 

  • Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ (Clin Res Ed) 315(7109):629–634

    Article  CAS  Google Scholar 

  • Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM (2010) Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer J Int Du Cancer 127(12):2893–2917. doi:10.1002/ijc.25516

    Article  CAS  Google Scholar 

  • Fondevila C, Metges JP, Fuster J, Grau JJ, Palacin A, Castells A, Volant A, Pera M (2004) p53 and VEGF expression are independent predictors of tumour recurrence and survival following curative resection of gastric cancer. Br J Cancer 90(1):206–215. doi:10.1038/sj.bjc.6601455

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Hwang TL, Lee LY, Wang CC, Liang Y, Huang SF, Wu CM (2010) Claudin-4 expression is associated with tumor invasion, MMP-2 and MMP-9 expression in gastric cancer. Exp Ther Med 1(5):789–797. doi:10.3892/etm.2010.116

    PubMed Central  PubMed  Google Scholar 

  • Kim BS, Cho SW, Min SK, Lee BH (2011) Differences in prognostic factors between early and advanced gastric cancer. Hepatogastroenterology 58(107–108):1032–1040

    PubMed  Google Scholar 

  • Kjellman M, Enberg U, Hoog A, Larsson C, Holst M, Farnebo LO, Sato H, Backdahl M (1999) Gelatinase A and membrane-type 1 matrix metalloproteinase mRNA: expressed in adrenocortical cancers but not in adenomas. World J Surg 23(3):237–242

    Article  CAS  PubMed  Google Scholar 

  • Kubben FJ, Sier CF, van Duijn W, Griffioen G, Hanemaaijer R, van de Velde CJ, van Krieken JH, Lamers CB, Verspaget HW (2006) Matrix metalloproteinase-2 is a consistent prognostic factor in gastric cancer. Br J Cancer 94(7):1035–1040. doi:10.1038/sj.bjc.6603041

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • McCawley LJ, Matrisian LM (2000) Matrix metalloproteinases: multifunctional contributors to tumor progression. Mol Med Today 6(4):149–156

    Article  CAS  PubMed  Google Scholar 

  • Moher D, Liberati A, Tetzlaff J, Altman DG (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 6(7):e1000097. doi:10.1371/journal.pmed.1000097

    Article  PubMed Central  PubMed  Google Scholar 

  • Monig SP, Baldus SE, Hennecken JK, Spiecker DB, Grass G, Schneider PM, Thiele J, Dienes HP, Holscher AH (2001) Expression of MMP-2 is associated with progression and lymph node metastasis of gastric carcinoma. Histopathology 39(6):597–602

    Article  CAS  PubMed  Google Scholar 

  • Mrena J, Wiksten JP, Nordling S, Kokkola A, Ristimaki A, Haglund C (2006) MMP-2 but not MMP-9 associated with COX-2 and survival in gastric cancer. J Clin Pathol 59(6):618–623. doi:10.1136/jcp.2005.033761

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Nomura H, Fujimoto N, Seiki M, Mai M, Okada Y (1996) Enhanced production of matrix metalloproteinases and activation of matrix metalloproteinase 2 (gelatinase A) in human gastric carcinomas. Int J Cancer 69(1):9–16. doi:10.1002/(sici)1097-0215(19960220)69:1<9:aid-ijc3>3.0.co;2-8

    Article  CAS  PubMed  Google Scholar 

  • Nordmann AJ, Kasenda B, Briel M (2012) Meta-analyses: what they can and cannot do. Swiss Med Wkly 142:w13518. doi:10.4414/smw.2012.13518

    PubMed  Google Scholar 

  • Parmar MK, Torri V, Stewart L (1998) Extracting summary statistics to perform meta-analyses of the published literature for survival endpoints. Stat Med 17(24):2815–2834

    Article  CAS  PubMed  Google Scholar 

  • Peng CW, Liu XL, Liu X, Li Y (2010) Co-evolution of cancer microenvironment reveals distinctive patterns of gastric cancer invasion: laboratory evidence and clinical significance. J Transl Med 8:101. doi:10.1186/1479-5876-8-101

    Article  PubMed Central  PubMed  Google Scholar 

  • Rundhaug JE (2005) Matrix metalloproteinases and angiogenesis. J Cell Mol Med 9(2):267–285

    Article  CAS  PubMed  Google Scholar 

  • Seshadri RA, Jayanand SB, Ranganathan R (2011) Prognostic factors in patients with node-negative gastric cancer: an Indian experience. World J Surg Oncol 9:48. doi:10.1186/1477-7819-9-48

    Article  PubMed Central  PubMed  Google Scholar 

  • Stang A (2010) Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol 25(9):603–605. doi:10.1007/s10654-010-9491-z

    Article  PubMed  Google Scholar 

  • Steels E, Paesmans M, Berghmans T, Branle F, Lemaitre F, Mascaux C, Meert AP, Vallot F, Lafitte JJ, Sculier JP (2001) Role of p53 as a prognostic factor for survival in lung cancer: a systematic review of the literature with a meta-analysis. Eur Respir J 18(4):705–719

    Article  CAS  PubMed  Google Scholar 

  • Stetler-Stevenson WG (2001) The role of matrix metalloproteinases in tumor invasion, metastasis, and angiogenesis. Surg Oncol Clin N Am 10 (2):383–392

    Google Scholar 

  • Sundblad A, Ricci L (1998) MMP-2 expression (type IV collagenase) in gastric cancer. Acta Gastroenterol Latinoam 28(4):287–290

    CAS  PubMed  Google Scholar 

  • Takahashi Y, Kitadai Y, Ellis LM, Bucana CD, Fidler IJ, Mai M (2002) Multiparametric in situ mRNA hybridization analysis of gastric biopsies predicts lymph node metastasis in patients with gastric carcinoma. Jpn J Cancer Res 93(11):1258–1265

    Article  CAS  PubMed  Google Scholar 

  • Wang G, Wang W, Zhou J, Yang X (2013) Correlation between telomerase activity and matrix metalloproteinases 2 expression in gastric cancer. Cancer Biomark 13(1):21–28. doi:10.3233/cbm-130332

    CAS  PubMed  Google Scholar 

  • Xing X, Tang YB, Yuan G, Wang Y, Wang J, Yang Y, Chen M (2013) The prognostic value of E-cadherin in gastric cancer: a meta-analysis. Int J Cancer 132(11):2589–2596. doi:10.1002/ijc.27947

    Article  CAS  PubMed  Google Scholar 

  • Yasui W, Hata J, Yokozaki H, Nakatani H, Ochiai A, Ito H, Tahara E (1988) Interaction between epidermal growth factor and its receptor in progression of human gastric carcinoma. Int J Cancer 41(2):211–217

    Article  CAS  PubMed  Google Scholar 

  • Zhao D, Xu H, Li K, Sun Z (2010) Prognostic factors for patients after curative resection for proximal gastric cancer. J Huazhong Univ Sci Technol Med Sci (4):530–535. doi:10.1007/s11596-010-0463-z

  • Zhou Y, Li G, Wu J, Zhang Z, Wu Z, Fan P, Hao T, Zhang X, Li M, Zhang F, Li Q, Lu B, Qiao L (2010) Clinicopathological significance of E-cadherin, VEGF, and MMPs in gastric cancer. Tumour Biol 31(6):549–558. doi:10.1007/s13277-010-0068-y

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by the National Nature Science Foundation of China, No. 81272698.

Conflict of interest

The authors have no conflict of interest.

Author information

Authors and Affiliations

  1. Department of General Surgery, Chinese People’s Liberation Army General Hospital, 28 Fuxing Road, Beijing, 100853, China

    Weisong Shen, Hongqing Xi, Bo Wei & Lin Chen

Authors
  1. Weisong Shen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hongqing Xi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Bo Wei
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Lin Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Lin Chen.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Shen, W., Xi, H., Wei, B. et al. The prognostic role of matrix metalloproteinase 2 in gastric cancer: a systematic review with meta-analysis. J Cancer Res Clin Oncol 140, 1003–1009 (2014). https://doi.org/10.1007/s00432-014-1630-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00432-014-1630-6

Keywords

Search

Navigation