Tumor Biology

, Volume 34, Issue 2, pp 735–741 | Cite as

RETRACTED ARTICLE: Matrix metalloproteinase 9 expression and prognosis in colorectal cancer: a meta-analysis

  • Chun-Yu Li
  • Peng Yuan
  • Shu-Sen Lin
  • Cheng-Fei Song
  • Wei-Yu Guan
  • Lu Yuan
  • Rong-Bin Lai
  • Ying Gao
  • Yan Wang
Research Article


Matrix metalloproteinase-9 (MMP-9) is an important member of the matrix metalloproteinase family and is considered to be involved in the invasion and metastasis of cancer cells. Many studies were published to assess the prognostic role of MMP-9 overexpression in patients with colorectal cancer, but the findings from those studies were inconsistent. We searched eligible studies in Pubmed, Embase, and Web of Science databases. Thirteen studies with a total of 2, 390 CRC patients were finally included into the meta-analysis. The pooled hazard ratios (HRs) with the corresponding 95 % confidence interval (95 % CIs) for overall and progression-free survival were calculated by using meta-analysis. There were nine studies with a total of 1,674 colorectal cancer patients relating the progression-free survival, and eight studies with a total of 1,379 colorectal cancer patients relating the overall survival. Overall, MMP-9 overexpression was associated with poorer progression-free survival in patients with colorectal cancer (fixed-effects HR 1.81, 95 % CI 1.48–2.20, P < 0.001; random-effects HR 1.92, 95 % CI 1.46–2.53, P < 0.001). In addition, MMP-9 overexpression was also associated with poorer overall survival in patients with colorectal cancer (fixed-effects HR 1.74, 95 % CI 1.39–2.19, P < 0.001; random-effects HR 1.78, 95 % CI 1.31–2.41, P < 0.001). MMP-9 expression is associated with the prognosis of patients with colorectal cancer, and patients with higher MMP-9 expression have poorer survival.


Matrix metalloproteinase-9 Colorectal cancer Survival Meta-analysis 


Conflicts of interest



  1. 1.
    Kessenbrock K, Plaks V, Werb Z. Matrix metalloproteinases: regulators of the tumor microenvironment. Cell. 2010;141:52–67.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Walther A, Johnstone E, Swanton C, Midgley R, Tomlinson I, Kerr D. Genetic prognostic and predictive markers in colorectal cancer. Nat Rev Cancer. 2009;9:489–99.CrossRefPubMedGoogle Scholar
  3. 3.
    Zhou Y, Li G, Wu J, Zhang Z, Wu Z, Fan P, et al. Clinicopathological significance of E-cadherin, VEGF, and MMPs in gastric cancer. Tumour Biol. 2010;31:549–58.CrossRefPubMedGoogle Scholar
  4. 4.
    Morrison CJ, Butler GS, Rodriguez D, Overall CM. Matrix metalloproteinase proteomics: substrates, targets, and therapy. Curr Opin Cell Biol. 2009;21:645–53.CrossRefPubMedGoogle Scholar
  5. 5.
    Page-McCaw A, Ewald AJ, Werb Z. Matrix metalloproteinases and the regulation of tissue remodelling. Nat Rev Mol Cell Biol. 2007;8:221–33.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Chu D, Zhao Z, Zhou Y, Li Y, Li J, Zheng J, et al. Matrix metalloproteinase-9 is associated with relapse and prognosis of patients with colorectal cancer. Ann Surg Oncol. 2012;19:318–25.CrossRefPubMedGoogle Scholar
  7. 7.
    Langers AM, Verspaget HW, Hawinkels LJ, Kubben FJ, van Duijn W, van der Reijden JJ, et al. Mmp-2 and mmp-9 in normal mucosa are independently associated with outcome of colorectal cancer patients. Br J Cancer. 2012;106:1495–8.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Unsal D, Akyurek N, Uner A, Erpolat OP, Han U, Akmansu M, et al. Gelatinase b expression as a prognostic factor in patients with stage II/III rectal carcinoma treated by postoperative adjuvant therapy. Am J Clin Oncol. 2008;31:55–63.CrossRefPubMedGoogle Scholar
  9. 9.
    Langers AM, Sier CF, Hawinkels LJ, Kubben FJ, van Duijn W, van der Reijden JJ, et al. Mmp-2 geno-phenotype is prognostic for colorectal cancer survival, whereas mmp-9 is not. Br J Cancer. 2008;98:1820–3.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Ogata Y, Matono K, Sasatomi T, Ishibashi N, Ohkita A, Mizobe T, et al. The mmp-9 expression determined the efficacy of postoperative adjuvant chemotherapy using oral fluoropyrimidines in stage II or III colorectal cancer. Cancer Chemother Pharmacol. 2006;57:577–83.CrossRefPubMedGoogle Scholar
  11. 11.
    Bendardaf R, Buhmeida A, Hilska M, Laato M, Syrjanen S, Syrjanen K, et al. Mmp-9 (gelatinase b) expression is associated with disease-free survival and disease-specific survival in colorectal cancer patients. Cancer Invest. 2010;28:38–43.CrossRefPubMedGoogle Scholar
  12. 12.
    Cho YR, Kwon HC, Suh SH, Lee JH, Kim SH, Choi HJ, et al. Expressions of matrix metalloproteinase-7 and −9 and their prognostic significances in rectal cancer. Cancer Res Treat. 2005;37:354–9.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Takeuchi T, Hisanaga M, Nagao M, Ikeda N, Fujii H, Koyama F, et al. The membrane-anchored matrix metalloproteinase (MMP) regulator RECK in combination with mmp-9 serves as an informative prognostic indicator for colorectal cancer. Clin Cancer Res. 2004;10:5572–9.CrossRefPubMedGoogle Scholar
  14. 14.
    Jensen SA, Vainer B, Bartels A, Brunner N, Sorensen JB. Expression of matrix metalloproteinase 9 (mmp-9) and tissue inhibitor of metalloproteinases 1 (timp-1) by colorectal cancer cells and adjacent stroma cells–associations with histopathology and patients outcome. Eur J Cancer. 2010;46:3233–42.CrossRefPubMedGoogle Scholar
  15. 15.
    Cho YB, Lee WY, Song SY, Shin HJ, Yun SH, Chun HK. Matrix metalloproteinase-9 activity is associated with poor prognosis in t3-t4 node-negative colorectal cancer. Hum Pathol. 2007;38:1603–10.CrossRefPubMedGoogle Scholar
  16. 16.
    Zhang Y, Guan XY, Dong B, Zhao M, Wu JH, Tian XY, Hao CY. Expression of MMP-9 and WAVE3 in colorectal cancer and its relationship to clinicopathological features. J Cancer Res Clin Oncol 2012Google Scholar
  17. 17.
    Zeng ZS, Huang Y, Cohen AM, Guillem JG. Prediction of colorectal cancer relapse and survival via tissue RNA levels of matrix metalloproteinase-9. J Clin Oncol. 1996;14:3133–40.CrossRefPubMedGoogle Scholar
  18. 18.
    Buhmeida A, Bendardaf R, Hilska M, Collan Y, Laato M, Syrjanen S, et al. Prognostic significance of matrix metalloproteinase-9 (MMP-9) in stage ii colorectal carcinoma. J Gastrointest Cancer. 2009;40:91–7.CrossRefPubMedGoogle Scholar
  19. 19.
    Parmar MK, Torri V, Stewart L. Extracting summary statistics to perform meta-analyses of the published literature for survival endpoints. Stat Med. 1998;17:2815–34.CrossRefPubMedGoogle Scholar
  20. 20.
    Tierney JF, Stewart LA, Ghersi D, Burdett S, Sydes MR. Practical methods for incorporating summary time-to-event data into meta-analysis. Trials. 2007;8:16.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Mantel N, Haenszel W. Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst. 1959;22:719–48.PubMedGoogle Scholar
  22. 22.
    DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7:177–88.CrossRefPubMedGoogle Scholar
  23. 23.
    Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ. 2003;327:557–60.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Cunningham D, Atkin W, Lenz HJ, Lynch HT, Minsky B, Nordlinger B, et al. Colorectal cancer. Lancet. 2010;375:1030–47.CrossRefPubMedGoogle Scholar
  25. 25.
    Fearon ER. Molecular genetics of colorectal cancer. Annu Rev Pathol. 2011;6:479–507.CrossRefPubMedGoogle Scholar
  26. 26.
    Des Guetz G, Uzzan B, Nicolas P, Cucherat M, Morere JF, Benamouzig R, et al. Microvessel density and VEGF expression are prognostic factors in colorectal cancer. Meta-analysis of the literature. Br J Cancer. 2006;94:1823–32.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Popat S, Matakidou A, Houlston RS. Thymidylate synthase expression and prognosis in colorectal cancer: a systematic review and meta-analysis. J Clin Oncol. 2004;22:529–36.CrossRefPubMedGoogle Scholar
  28. 28.
    Koskensalo S, Louhimo J, Nordling S, Hagstrom J, Haglund C. Mmp-7 as a prognostic marker in colorectal cancer. Tumour Biol. 2011;32:259–64.CrossRefPubMedGoogle Scholar
  29. 29.
    Fang YJ, Lu ZH, Wang F, Wu XJ, Li LR, Zhang LY, et al. Prognostic impact of ERbeta and MMP7 expression on overall survival in colon cancer. Tumour Biol. 2010;31:651–8.CrossRefPubMedGoogle Scholar
  30. 30.
    Lampropoulos P, Zizi-Sermpetzoglou A, Rizos S, Kostakis A, Nikiteas N, Papavassiliou AG. Prognostic significance of transforming growth factor beta (TGF-beta) signaling axis molecules and E-cadherin in colorectal cancer. Tumour Biol. 2012;33:1005–14.CrossRefPubMedGoogle Scholar
  31. 31.
    Mott JD, Werb Z. Regulation of matrix biology by matrix metalloproteinases. Curr Opin Cell Biol. 2004;16:558–64.CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Parks WC, Wilson CL, Lopez-Boado YS. Matrix metalloproteinases as modulators of inflammation and innate immunity. Nat Rev Immunol. 2004;4:617–29.CrossRefPubMedGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2012

Authors and Affiliations

  • Chun-Yu Li
    • 1
  • Peng Yuan
    • 1
  • Shu-Sen Lin
    • 1
  • Cheng-Fei Song
    • 1
  • Wei-Yu Guan
    • 1
  • Lu Yuan
    • 1
  • Rong-Bin Lai
    • 1
  • Ying Gao
    • 2
  • Yan Wang
    • 1
  1. 1.Anorectal DepartmentThe Fourth Affiliated Hospital of China Medical UniversityShenyangChina
  2. 2.Department of PathologyThe Fourth Affiliated Hospital of China Medical UniversityShenyangChina

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