Matrix metalloproteinase 9 expression and survival of patients with osteosarcoma: a meta‐analysis

Several studies have evaluated the effect of matrix metalloproteinase-9 (MMP-9) expression on the overall survival of patients with osteosarcoma, but the results remain conflicting. To examine the prognostic significance of MMP-9 expression in osteosarcoma risk, we conducted this meta-analysis to systematically review the published studies. We searched the commonly used electronic databases updated to September 2013 for relevant studies which evaluated the correction between MMP-9 expression and survival of patients with osteosarcoma. Overall, a total of eight studies including 437 cases were screened out. No significant heterogeneity was observed between studies. The MMP-9 was expressed in 73.9% (323/437) of cases, and the results showed that MMP-9 expression was associated with increased mortality rate of osteosarcoma during the follow-up (risk ratio = 2.79, 95% confidence interval, CI = 1.96-3.97, P < 0.00001). By ethnicity analysis, a significant correction was also found between MMP-9 expression and osteosarcoma risk among Asian and non-Asian population (P < 0.001), indicating that MMP-9 was an indicator of prognosis of osteosarcoma. In conclusion, this meta-analysis indicated that MMP-9 expression might be a biomarker of poor prognosis for patients with osteosarcoma. However, the prognostic value of MMP-9 on survival of osteosarcoma patients still needs further large-scale trials to be clarified.

[1]  石川 聡,et al.  Matrix Metalloproteinase , 1997, Definitions.

[2]  M. Collins,et al.  Matrix metalloproteinase-9 (MMP-9) expression in childhood osseous osteosarcoma. , 1998, Medical and pediatric oncology.

[3]  Y. Konishi,et al.  Overexpression of matrix metalloproteinase (MMP)-9 correlates with metastatic potency of spontaneous and 4-hydroxyaminoquinoline 1-oxide (4-HAQO)-induced transplantable osteosarcomas in rats. , 1999, Cancer letters.

[4]  Tae Sook Kim,et al.  Correlation between expression of matrix metalloproteinase-2 (MMP-2), and matrix metalloproteinase-9 (MMP-9) and angiogenesis in colorectal adenocarcinoma. , 1999, Journal of Korean medical science.

[5]  in vivo factor by endothelial cells and monocytes and promotes angiogenesis Ligation of CD 40 induces the expression of vascular endothelial growth , 2000 .

[6]  R. Grimer,et al.  Stage-IIB osteosarcomas around the knee. A study of MMP-9 in surviving tumour cells. , 2002, The Journal of bone and joint surgery. British volume.

[7]  W. Winkelmann,et al.  Prognostic factors in high-grade osteosarcoma of the extremities or trunk: an analysis of 1,702 patients treated on neoadjuvant cooperative osteosarcoma study group protocols. , 2002, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[8]  G. Rogers,et al.  Prognostic factors. , 2002, Dermatologic clinics.

[9]  W. Winkelmann,et al.  Prognostic factors in high-grade osteosarcoma of the extremities or trunk: an analysis of 1,702 patients treated on neoadjuvant cooperative osteosarcoma study group protocols. , 2002, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[10]  O. Fodstad,et al.  Matrix metalloproteinases participate in osteosarcoma invasion. , 2005, The Journal of surgical research.

[11]  Maya Ram,et al.  Matrix Metalloproteinase-9 and Autoimmune Diseases , 2006, Journal of Clinical Immunology.

[12]  Ye Zhaoming The expression of vascular endothelial growth factor,matrix metalloproteinases 2,9 in osteosarcoma , 2006 .

[13]  N. Ishiguro,et al.  Increased expression of membrane-type matrix metalloproteinase-1 is correlated with poor prognosis in patients with osteosarcoma. , 2006, International journal of oncology.

[14]  N. Jaffe Osteosarcoma: review of the past, impact on the future. The American experience. , 2009, Cancer treatment and research.

[15]  C. Overall,et al.  Matrix metalloproteinase proteomics: substrates, targets, and therapy. , 2009, Current opinion in cell biology.

[16]  Hui Gao,et al.  Smoothened as a new therapeutic target for human osteosarcoma , 2010, Molecular Cancer.

[17]  G. Ottaviani,et al.  The epidemiology of osteosarcoma. , 2009, Cancer treatment and research.

[18]  N. Mukaida,et al.  Absence of IFN‐gamma accelerates thrombus resolution through enhanced MMP‐9 and VEGF expression , 2009 .

[19]  R. Gorlick,et al.  Osteosarcoma: a review of diagnosis, management, and treatment strategies. , 2010, Clinical advances in hematology & oncology : H&O.

[20]  Young-Chae Chang,et al.  Melittin suppresses PMA-induced tumor cell invasion by inhibiting NF-κB and AP-1-dependent MMP-9 expression , 2010, Molecules and cells.

[21]  E. Gershtein,et al.  Matrix Metalloproteinases 2, 7, 9 and Tissue Inhibitor of Matrix Metalloproteinase-1 in the Sera of Patients with Bone Tumors , 2010, Bulletin of Experimental Biology and Medicine.

[22]  Z. Werb,et al.  Matrix Metalloproteinases: Regulators of the Tumor Microenvironment , 2010, Cell.

[23]  R. Gilbert,et al.  Expression of matrix metalloproteinase‐1, ‐7, ‐9, ‐13, Ki‐67, and HER‐2 in epithelial‐myoepithelial salivary gland cancer , 2009, Head & neck.

[24]  K. Wood,et al.  The kinase Mirk is a potential therapeutic target in osteosarcoma. , 2010, Carcinogenesis.

[25]  B. V. van Royen,et al.  Molecular alterations as target for therapy in metastatic osteosarcoma: a review of literature , 2011, Clinical & Experimental Metastasis.

[26]  Jason L Johnson,et al.  Matrix Metalloproteinase (MMP)-3 Activates MMP-9 Mediated Vascular Smooth Muscle Cell Migration and Neointima Formation in Mice , 2011, Arteriosclerosis, thrombosis, and vascular biology.

[27]  X. Diao,et al.  Regulation of VEGF, MMP‐9 and metastasis by CXCR4 in a prostate cancer cell line , 2011, Cell biology international.

[28]  S. Fan,et al.  Overexpression of matrix metalloproteinase-12 (MMP-12) correlates with poor prognosis of hepatocellular carcinoma. , 2011, European journal of cancer.

[29]  S. Poletajew,et al.  Current concepts on pathogenesis and biology of metastatic osteosarcoma tumors. , 2011, Ortopedia, traumatologia, rehabilitacja.

[30]  N. Mukaida,et al.  Absence of IFN-γ accelerates thrombus resolution through enhanced MMP-9 and VEGF expression in mice. , 2011, The Journal of clinical investigation.

[31]  T. Salo,et al.  Expression of matrix metalloproteinases-2, -8, -13, -26, and tissue inhibitors of metalloproteinase-1 in human osteosarcoma. , 2011, Surgical oncology.

[32]  S. Seo,et al.  ERK5 regulates invasiveness of osteosarcoma by inducing MMP‐9 , 2012, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[33]  Jingnan Shen,et al.  High serum alkaline phosphatase cooperating with MMP-9 predicts metastasis and poor prognosis in patients with primary osteosarcoma in Southern China , 2012, World Journal of Surgical Oncology.

[34]  R. de Caterina,et al.  Mediterranean diet polyphenols reduce inflammatory angiogenesis through MMP-9 and COX-2 inhibition in human vascular endothelial cells: a potentially protective mechanism in atherosclerotic vascular disease and cancer. , 2012, Archives of biochemistry and biophysics.

[35]  S. Babykutty,et al.  Nimbolide retards tumor cell migration, invasion, and angiogenesis by downregulating MMP‐2/9 expression via inhibiting ERK1/2 and reducing DNA‐binding activity of NF‐κB in colon cancer cells , 2012, Molecular carcinogenesis.

[36]  X. Yu,et al.  Prognostic significance of VEGF expression in osteosarcoma: a meta-analysis , 2013, Tumor Biology.

[37]  Xiaoyan Wen,et al.  Matrix metalloproteinase 2 expression and survival of patients with osteosarcoma: a meta-analysis , 2013, Tumor Biology.

[38]  L. Liu,et al.  RNAi-mediated knockdown of relaxin decreases in vitro proliferation and invasiveness of osteosarcoma MG-63 cells by inhibition of MMP-9. , 2013, European review for medical and pharmacological sciences.

[39]  P. E. Van den Steen,et al.  Biochemistry and molecular biology of gelatinase B or matrix metalloproteinase-9 (MMP-9): The next decade , 2013, Critical reviews in biochemistry and molecular biology.

[40]  Shun-Fa Yang,et al.  Selaginella tamariscina (Beauv.) possesses antimetastatic effects on human osteosarcoma cells by decreasing MMP-2 and MMP-9 secretions via p38 and Akt signaling pathways. , 2013, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.