Abstract
Matrix metalloproteinase-21 (MMP-21) has been shown to enhance tumor invasion and metastasis ability in some solid tumors. In the present study, we investigated the expression of MMP-21 as well as its association with overall survival of gastric cancer patients. MMP-21 expression was investigated in 296 cases of gastric cancer by immunohistochemistry assay. Statistical analysis was utilized to evaluate the association of MMP-21 expression with overall survival of patients. MMP-21 expression was proved to be increased in gastric cancer compared with that in normal tissues (P < 0.05). It was also proved MMP-21 expression was associated with tumor invasion, metastasis and TNM stage (P < 0.001). MMP-21 expression was showed to be associated with overall survival of gastric cancer patients for patients with tumor of higher MMP-21 expression tend to have worse overall survival (P < 0.001). Multivariate analysis proved MMP-21 to be an independent prognostic factor for overall survival of gastric cancer patients (P < 0.001). These results suggested the potential role of MMP-21 in progression of human gastric cancer. It might also be a novel molecular marker to predict overall survival of patients with gastric cancer.
Similar content being viewed by others
References
Siegel R, Naishadham D, Jemal A. Cancer statistics. CA Cancer J Clin. 2012;62:10–29.
Jemal A, Bray F, Center MM, et al. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90.
Yang L. Incidence and mortality of gastric cancer in China. World J Gastroenterol. 2006;12:17–20.
Parsons SL, Watson SA, Brown PD, et al. Matrix metalloproteinases. Br J Surg. 1997;84:160–6.
Curran S, Murray GI. Matrix metalloproteinases: molecular aspects of their roles in tumour invasion and metastasis. Eur J Cancer. 2000;36:1621–30.
Nagase H, Woessner JF Jr. Matrix metalloproteinases. J Biol Chem. 1999;30(274):21491–4.
Nelson AR, Fingleton B, Rothenberg ML, et al. Matrix metalloproteinases: biologic activity and clinical implications. J Clin Oncol. 2000;18:1135–49.
Park HI, Ni J, Gerkema FE, et al. Identification and characterization of human endometase (matrix metalloproteinase-26) from endometrial tumor. J Biol Chem. 2000;275:20540–4.
Stetler-Stevenson WG. The role of matrix metalloproteinases in tumor invasion, metastasis and angiogenesis. Surg Oncol Clin N Am. 2001;10:383–92.
Hidalgo M, Eckhardt SG. Development of matrix metalloproteinase inhibitors in cancer therapy. J Natl Cancer Inst. 2001;93:178–93.
Curran S, Murray GI. Matrix metalloproteinases in tumour invasion and metastasis. J Pathol. 1999;189:300–8.
Chambers AF, Matrisian LM. Changing views of the role of matrix metalloproteinases in metastasis. J Natl Cancer Inst. 1997;89:1260–70.
Reis ST, Leite KR, Piovesan LF, et al. Increased expression of MMP-9 and IL-8 are correlated with poor prognosis of bladder cancer. BMC Urol. 2012;12:18.
Song N, Sung H, Choi JY, et al. Preoperative serum levels of matrix metalloproteinase-2 (MMP-2) and survival of breast cancer among Korean women. Cancer Epidemiol Biomarkers Prev. 2012 Jun 5.
Ng KT, Qi X, Kong KL, et al. Overexpression of matrix metalloproteinase-12 (MMP-12) correlates with poor prognosis of hepatocellular carcinoma. Eur J Cancer. 2011;47:2299–305.
Chen R, Cui J, Xu C, et al. The Significance of MMP-9 Over MMP-2 in HCC invasiveness and recurrence of hepatocellular carcinoma after curative resection. Ann Surg Oncol. 2011 Jun 17.
Barresi V, Vitarelli E, Tuccari G, et al. MMP-9 expression in meningiomas: a prognostic marker for recurrence risk? J Neurooncol. 2011;102:189–96.
Chen T, Zhu J. Evaluation of EMMPRIN and MMP-2 in the prognosis of primary cutaneous malignant melanoma. Med Oncol. 2010;27:1185–91.
Zeng ZS, Huang Y, Cohen AM, et al. Prediction of colorectal cancer relapse and survival via tissue RNA levels of matrix metalloproteinase-9. J Clin Oncol. 1996;14:3133–40.
Fujimoto D, Hirono Y, Goi T, et al. Prognostic value of protease-activated receptor-1 (PAR-1) and matrix metalloproteinase-1 (MMP-1) in gastric cancer. Anticancer Res. 2008;28:847–54.
Partyka R, Gonciarz M, Jałowiecki P, et al. VEGF and metalloproteinase 2 (MMP-2) expression in gastric cancer tissue. Med Sci Monit. 2012; 18: BR130–4.
Noh S, Jung JJ, Jung M, et al. MMP-2 as a putative biomarker for carcinomatosis in gastric cancer. Hepatogastroenterology. 2011;58:2015–9.
Koskensalo S, Mrena J, Wiksten JP, et al. MMP-7 overexpression is an independent prognostic marker in gastric cancer. Tumour Biol. 2010;31:149–55.
Al-Batran SE, Pauligk C, Wirtz R, et al. The validation of matrix metalloproteinase-9 mRNA gene expression as a predictor of outcome in patients with metastatic gastric cancer. Ann Oncol. 2011 Nov 23.
Yan D, Dai H, Liu JW. Serum levels of MMP-11 correlate with clinical outcome in Chinese patients with advanced gastric adenocarcinoma. BMC Cancer. 2011;11:151.
Suomela S, Koljonen V, Skoog T, et al. Expression of MMP-10, MMP-21, MMP-26, and MMP-28 in merkel cell carcinoma. Virchows Arch. 2009;455:495–503.
Boyd S, Virolainen S, Pärssinen J, et al. MMP-10 (Stromelysin-2) and MMP-21 in human and murine squamous cell cancer. Exp Dermatol. 2009;18:1044–52.
Germani RM, Civantos FJ, Elgart G, et al. Molecular markers of micrometastasis in oral cavity carcinomas. Otolaryngol Head Neck Surg. 2009;141:52–8.
Qiu W, Zhou G, Zhai Y, et al. No association of MMP-7, MMP-8, and MMP-21 polymorphisms with the risk of hepatocellular carcinoma in a Chinese population. Cancer Epidemiol Biomarkers Prev. 2008;17:2514–8.
Bister V, Skoog T, Virolainen S, et al. Increased expression of matrix metalloproteinases-21 and -26 and TIMP-4 in pancreatic adenocarcinoma. Mod Pathol. 2007;20:1128–40.
Shagisultanova EI, Novikova IA, Sidorenko YS, et al. The matrix metalloproteinase-21 gene 572C/T polymorphism and the risk of breast cancer. Anticancer Res. 2004;24:199–201.
Ahokas K, Lohi J, Illman SA, et al. Matrix metalloproteinase-21 is expressed epithelially during development and in cancer and is up-regulated by transforming growth factor-beta1 in keratinocytes. Lab Invest. 2003;83:1887–99.
Wu T, Li Y, Liu X, et al. Identification of high-risk stage II and stage III colorectal cancer by analysis of MMP-21 expression. J Surg Oncol. 2011;104:787–91.
Rhodes A, Jasani B, Barnes DM, et al. Reliability of immunohistochemical demonstration of oestrogen receptors in routine practice: interlaboratory variance in the sensitivity of detection and evaluation of scoring systems. J Clin Pathol. 2000;53:125–30.
Conflict of interest
We declared no conflict of interest.
Author information
Authors and Affiliations
Corresponding authors
Additional information
Tao Wu and Yi Li contributed equally to this study.
Rights and permissions
About this article
Cite this article
Wu, T., Li, Y., Lu, J. et al. Increased MMP-21 expression is associated with poor overall survival of patients with gastric cancer. Med Oncol 30, 323 (2013). https://doi.org/10.1007/s12032-012-0323-8
Received:
Accepted:
Published:
DOI: https://doi.org/10.1007/s12032-012-0323-8