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Cancer Biomarkers: Section A of Disease Markers logoLink to Cancer Biomarkers: Section A of Disease Markers
. 2016 Apr 13;16(4):599–607. doi: 10.3233/CBM-160601

Elevated serum levels of MMP-11 correlate with poor prognosis in colon cancer patients

Li Pang a, Da-Wei Wang a, Nan Zhang a, Da-Hai Xu a, Xiang-Wei Meng b,*
PMCID: PMC13016514  PMID: 27002762

Abstract

BACKGROUND:

Matrix metalloproteinase 11 (MMP11) has been shown to play a key role in human tumor progression and indicates poor clinical outcome in cancer patients.

OBJECTIVE:

The current study aimed to evaluate the relationship between serum levels of MMP-11 and prognosis in colon cancer patients.

METHODS:

Serum levels of MMP-11 were determined in 92 colon cancer patients and 92 healthy individuals using an enzyme-linked immunosorbent assay (ELISA). Associations between serum MMP-11 levels and clinicopathological characteristics of the patients and their outcomes were investigated. Survival analyses were performed to measure the 5-year overall survival (OS) and disease-free survival (DFS).

RESULTS:

Serum MMP-11 levels were substantially higher in colon cancer patients than in healthy controls. Moreover, serum MMP-11 levels were significantly higher in patients with advanced T status, lymph node metastasis, distant metastasis, and a higher TNM stage. Elevated serum levels of MMP-11 were identified as an independent prognostic factor for 5-year mortality and adverse events associated with colon cancer. Multivariate Cox regression analysis identified the serum MMP-11 level as an independent predictor of OS and DFS.

CONCLUSION:

Our study established that high serum levels of MMP-11 are associated with poor clinical outcome and may serve as a prognostic biomarker in colon cancer patients.

Keywords: Matrix metalloproteinase 11, colon cancer, prognosis, biomarker

Full Text

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References

  • [1]. Andarawewa K.L., Boulay A., Masson W., Mathelin C., Stoll I., Tomasetto C., Chenard M.P., Gintz M., Bellocq J.P. and Rio M.C., Dual stromelysin-3 function during natural mouse mammary tumor virus-ras tumor progression, Cancer Research 63 (2003), 5844-5849. [PubMed] [Google Scholar]
  • [2]. Bartolome R.A., Ferreiro S., Miquilena-Colina M.E., Martinez-Prats L., Soto-Montenegro M.L., Garcia-Bernal D., Vaquero J.J., Agami R., Delgado R., Desco M., Sanchez-Mateos P. and Teixido J., The Chemokine Receptor CXCR4 and the Metalloproteinase MT1-MMP Are Mutually Required during Melanoma Metastasis to Lungs, American Journal of Pathology 174 (2009), 602-612. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [3]. Boulay A., Masson R., Chenard M.P., El Fahime M., Cassard L., Bellocq J.P., Sautes-Fridman C., Basset P. and Rio M.C., High cancer cell death in syngeneic tumors developed in host mice deficient for the stromelysin-3 matrix metalloproteinase, Cancer Research 61 (2001), 2189-2193. [PubMed] [Google Scholar]
  • [4]. Delebecq T.J., Porte H., Zerimech F., Copin M.C., Gouyer V., Dacquembronne E., Balduyck M., Wurtz A. and Huet G., Overexpression level of stromelysin 3 is related to the lymph node involvement in non-small cell lung cancer, Clinical Cancer Research 6 (2000), 1086-1092. [PubMed] [Google Scholar]
  • [5]. Deng H., Guo R.F., Li W.M., Zhao M. and Lu Y.Y., Matrix metalloproteinase 11 depletion inhibits cell proliferation in gastric cancer cells, Biochemical and Biophysical Research Communications 326 (2005), 274-281. [DOI] [PubMed] [Google Scholar]
  • [6]. Duffy M.J., Maguire T.M., Hill A., McDermott E. and O'Higgins N., Metalloproteinases: role in breast carcinogenesis, invasion and metastasis, Breast Cancer Research 2 (2000), 252-257. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [7]. Edge S.B. and Compton C.C., The American Joint Committee on Cancer: the 7th Edition of the AJCC Cancer Staging Manual and the Future of TNM, Annals of Surgical Oncology 17 (2010), 1471-1474. [DOI] [PubMed] [Google Scholar]
  • [8]. Escaff S., Fernandez J.M., Gonzalez L.O., Suarez A., Gonzalez-Reyes S., Gonzalez J.M. and Vizoso F.J., Study of matrix metalloproteinases and their inhibitors in prostate cancer, British Journal of Cancer 102 (2010), 922-929. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [9]. Hsin C.-H., Chen M.-K., Tang C.-H., Lin H.-P., Chou M.-Y., Lin C.-W. and Yang S.-F., High Level of Plasma Matrix Metalloproteinase-11 Is Associated with Clinicopathological Characteristics in Patients with Oral Squamous Cell Carcinoma, Plos One 9 (2014), e113129. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [10]. Jemal A., Bray F., Center M.M., Ferlay J., Ward E. and Forman D., Global Cancer Statistics, Ca-a Cancer Journal for Clinicians 61 (2011), 69-90. [DOI] [PubMed] [Google Scholar]
  • [11]. Jia L., Wang S., Cao J., Zhou H., Wei W. and Zhang J., siRNA targeted against matrix metalloproteinase 11 inhibits the metastatic capability of murine hepatocarcinoma cell Hca-F to lymph nodes, International Journal of Biochemistry & Cell Biology 39 (2007), 2049-2062. [DOI] [PubMed] [Google Scholar]
  • [12]. Kren L., Goncharuk V.N., Krenova Z., Stratil D., Hermanova M., Skrickova J., Sheehan C.E. and Ross J.S., Expression of matrix metalloproteinases 3, 10 and 11 (stromelysins 1, 2 and 3) and matrix metalloproteinase 7 (matrilysin) by cancer cells in non-small cell lung neoplasms. Clinicopathologic studies, Ceskoslovenska patologie 42 (2006), 16-9. [PubMed] [Google Scholar]
  • [13]. Min K.-W., Kim D.-H., Do S.-I., Pyo J.-S., Kim K., Chae S.W., Sohn J.H., Oh Y.-H., Kim H.J., Choi S.H., Choi Y.J. and Park C.H., Diagnostic and Prognostic Relevance of MMP-11 Expression in the Stromal Fibroblast-Like Cells Adjacent to Invasive Ductal Carcinoma of the Breast, Annals of Surgical Oncology 20 (2013), S433-S442. [DOI] [PubMed] [Google Scholar]
  • [14]. Moss L.A.S., Jensen-Taubman S. and Stetler-Stevenson W.G., Matrix Metalloproteinases Changing Roles in Tumor Progression and Metastasis, American Journal of Pathology 181 (2012), 1895-1899. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [15]. Nonsrijun N., Mitchai J., Brown K., Leksomboon R. and Tuamsuk P., Overexpression of Matrix Metalloproteinase 11 in Thai Prostatic Adenocarcinoma is Associated with Poor Survival, Asian Pacific Journal of Cancer Prevention 14 (2013), 3331-3335. [DOI] [PubMed] [Google Scholar]
  • [16]. Pedersen G., Saermark T., Kirkegaard T. and Brynskov J., Spontaneous and cytokine induced expression and activity of matrix metalloproteinases in human colonic epithelium, Clinical and Experimental Immunology 155 (2009), 257-265. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [17]. Porte H., Chastre E., Prevot S., Nordlinger B., Empereur S., Basset P., Chambon P. and Gespach C., Neoplastic progression of human colorectal-cancer is associated with overexpression of the stromelysin-3 AND BM-40/Sparc genes, International Journal of Cancer 64 (1995), 70-75. [DOI] [PubMed] [Google Scholar]
  • [18]. Roscilli G., Cappelletti M., De Vitis C., Ciliberto G., Di Napoli A., Ruco L., Mancini R. and Aurisicchio L., Circulating MMP11 and specific antibody immune response in breast and prostate cancer patients, Journal of Translational Medicine 12 (2014), 54. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [19]. Soni S., Mathur M., Shukla N.K., Deo S.V.S. and Ralfhan R., Stromelysin-3 expression is an early event in human oral tumorigenesis, International Journal of Cancer 107 (2003), 309-316. [DOI] [PubMed] [Google Scholar]
  • [20]. Stojic J., Hagemann C., Haas S., Herbold C., Kuehnel S., Gerngras S., Roggendorf W., Roosen K. and Vince G.H., Expression of matrix metalloproteinases MMP-1, MMP-11 and MMP-19 is correlated with the WHO-grading of human malignant gliomas, Neuroscience Research 60 (2008), 40-49. [DOI] [PubMed] [Google Scholar]
  • [21]. Tejpar S., Bertagnolli M., Bosman F., Lenz H.-J., Garraway L., Waldman F., Warren R., Bild A., Collins-Brennan D., Hahn H., Harkin D.P., Kennedy R., Ilyas M., Morreau H., Proutski V., Swanton C., Tomlinson I., Delorenzi M., Fiocca R., Van Cutsem E. and Roth A., Prognostic and Predictive Biomarkers in Resected Colon Cancer: Current Status and Future Perspectives for Integrating Genomics into Biomarker Discovery, Oncologist 15 (2010), 390-404. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [22]. Thewes M., Pohlmann G., Atkinson M., Mueller J., Putz B. and Hofler H., Stromelysin-3 (ST-3) mRNA expression in colorectal carcinomas - Localization and clinicopathologic correlations, Diagnostic Molecular Pathology 5 (1996), 284-290. [DOI] [PubMed] [Google Scholar]
  • [23]. Thorns V., Walter G.F. and Thorns C., Expression of MMP-2, MMP-7, MMP-9, MMP-10 and MMP-11 in human astrocytic and oligodendroglial gliomas, Anticancer Research 23 (2003), 3937-3944. [PubMed] [Google Scholar]
  • [24]. Vazquez-Ortiz G., Pina-Sanchez P., Vazquez K., Duenas A., Taja L., Mendoza P., Garcia J.A. and Salcedo M., Overexpression of cathepsin f, matrix metalloproteinases 11 and 12 in cervical cancer, Bmc Cancer 5 (2005), 68. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [25]. Wasenius V.M., Hemmer S., Kettunen E., Knuutila S., Franssila K. and Joensuu H., Hepatocyte growth factor receptor, matrix metalloproteinase-11, tissue inhibitor of metalloproteinase-1, and fibronectin are up-regulated in papillary thyroid carcinoma: A cDNA and tissue microarray study, Clinical Cancer Research 9 (2003), 68-75. [PubMed] [Google Scholar]
  • [26]. Weitz J., Koch M., Debus J., Hohler T., Galle P.R. and Buchler M.W., Colorectal cancer, Lancet 365 (2005), 153-165. [DOI] [PubMed] [Google Scholar]
  • [27]. Yan D., Dai H. and Liu J.-W., Serum levels of MMP-11 correlate with clinical outcome in Chinese patients with advanced gastric adenocarcinoma, Bmc Cancer 11 (2011), 165. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [28]. Zhao Z.-S., Chu Y.-Q., Ye Z.-Y., Wang Y.-Y. and Tao H.-Q., Overexpression of matrix metalloproteinase 11 in human gastric carcinoma and its clinicopathologic significance, Human Pathology 41 (2010), 686-696. [DOI] [PubMed] [Google Scholar]

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