Abstract
Messenger RNA (mRNA) acts as template for protein synthesis. The matrix metalloproteinase-7 (MMP-7) protein and its mRNA expression have been suggested to be involved in the development of various diseases and cancers. We aimed to study associations between the MMP-7 protein and mRNA expression in gastric carcinoma (GC) patients. We searched in the Science Citation Index, the Cochrane Library, PubMed, Embase, CINAHL, Current Contents Index, and several Chinese databases. Studies were pooled and odds ratios and their corresponding 95 % confidence intervals were calculated. Subgroup analyses and publication bias detection were also conducted. Statistical analysis was performed via Version 12.0 STATA software. An updated meta-analysis based on 16 independent cohort studies was performed to investigate this association. The study suggests that significant differences in MMP-7 protein levels were observed in tumor–node–metastasis (TNM) I–II vs. III–IV (odds radio (OR) = 3.19, 95 % confidence interval (95%CI) = 1.59∼6.41, P = 0.001), in T1-2 vs. T3-4 invasive grade (OR = 1.82, 95%CI = 1.07∼3.12, P = 0.028), and in distant metastasis-positive vs. metastasis-negative samples (OR = 3.14, 95%CI = 1.05∼9.35, P = 0.040). Increased MMP-7 mRNA levels were found to be significantly correlated with invasive grade (T3-4 vs. T1-2: OR = 5.61, 95%CI = 2.64∼11.95, P < 0.001) and in the lymph node (LN) metastasis (positive vs. negative: OR = 7.08, 95%CI = 4.20∼11.93, P < 0.001) group. Country subgroup analysis yielded significantly different estimates in the protein expression of MMP-7 of all experimental groups. MMP-7 mRNA levels were increased in LN metastasis-positive GC in contrast to metastasis-negative in China and Korea (all P < 0.05); this was not shown in Japan (P > 0.05). Higher protein and mRNA levels of MMP-7 were statistically associated with aggressive LN metastasis, advanced TNM stage, and invasion in GC patients; MMP-7 can thus potentially serve as a useful biomarker in determining GC progression and prognosis.
Similar content being viewed by others
References
Fanelli MF, Chinen LT, Begnami MD, Costa Jr WL, Fregnami JH, Soares FA, et al. The influence of transforming growth factor-alpha, cyclooxygenase-2, matrix metalloproteinase (MMP)-7, MMP-9 and CXCR4 proteins involved in epithelial-mesenchymal transition on overall survival of patients with gastric cancer. Histopathology. 2012;61(2):153–61.
Meng XY, Zhou CH, Ma J, Jiang C, Ji P. Expression of interleukin-17 and its clinical significance in gastric cancer patients. Med Oncol. 2012;29(5):3024–8.
Zhang X, Zheng L, Sun Y, Zhang X. Analysis of the association of interleukin-17 gene polymorphisms with gastric cancer risk and interaction with Helicobacter pylori infection in a Chinese population. Tumour Biol. 2014;35(2):1575–80.
Okayama H, Kumamoto K, Saitou K, Hayase S, Kofunato Y, Sato Y, et al. CD44v6, MMP-7 and nuclear Cdx2 are significant biomarkers for prediction of lymph node metastasis in primary gastric cancer. Oncol Rep. 2009;22(4):745–55.
Chen JQ, Zhan WH, He YL, Peng JS, Wang JP, Cai SR, et al. Expression of heparanase gene, CD44v6, MMP-7 and nm23 protein and their relationship with the invasion and metastasis of gastric carcinomas. World J Gastroenterol. 2004;10(6):776–82.
Yoshikawa T, Yanoma S, Tsuburaya A, Kobayashi O, Sairenji M, Motohashi H, et al. Expression of MMP-7 and MT1-MMP in peritoneal dissemination of gastric cancer. Hepatogastroenterology. 2006;53(72):964–7.
Koskensalo S, Mrena J, Wiksten JP, Nordling S, Kokkola A, Hagstrom J, et al. MMP-7 overexpression is an independent prognostic marker in gastric cancer. Tumour Biol. 2010;31(3):149–55.
Tahara T, Shibata T, Nakamura M, Yamashita H, Yoshioka D, Okubo M, et al. Association between IL-17A, −17F and MIF polymorphisms predispose to CpG island hyper-methylation in gastric cancer. Int J Mol Med. 2010;25(3):471–7.
Kitoh T, Yanai H, Saitoh Y, Nakamura Y, Matsubara Y, Kitoh H, et al. Increased expression of matrix metalloproteinase-7 in invasive early gastric cancer. J Gastroenterol. 2004;39(5):434–40.
Swarnakar S, Paul S, Singh LP, Reiter RJ. Matrix metalloproteinases in health and disease: regulation by melatonin. J Pineal Res. 2011;50(1):8–20.
Bauvois B. New facets of matrix metalloproteinases MMP-2 and MMP-9 as cell surface transducers: outside-in signaling and relationship to tumor progression. Biochim Biophys Acta. 2012;1825(1):29–36.
Koskensalo S, Louhimo J, Nordling S, Hagstrom J, Haglund C. MMP-7 as a prognostic marker in colorectal cancer. Tumour Biol. 2011;32(2):259–64.
Bourboulia D, Stetler-Stevenson WG. Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs): positive and negative regulators in tumor cell adhesion. Semin Cancer Biol. 2010;20(3):161–8.
Achyut BR, Ghoshal UC, Moorchung N, Mittal B. Transforming growth factor-B1 and matrix metalloproteinase-7 promoter variants induce risk for Helicobacter pylori-associated gastric precancerous lesions. DNA Cell Biol. 2009;28(6):295–301.
Lin MC, Wang FY, Kuo YH, Tang FY. Cancer chemopreventive effects of lycopene: suppression of MMP-7 expression and cell invasion in human colon cancer cells. J Agric Food Chem. 2011;59(20):11304–18.
Yang JD, Nakamura I, Roberts LR. The tumor microenvironment in hepatocellular carcinoma: current status and therapeutic targets. Semin Cancer Biol. 2011;21(1):35–43.
Zhou JH, Zhang B, Kernstine KH, Zhong L. Autoantibodies against MMP-7 as a novel diagnostic biomarker in esophageal squamous cell carcinoma. World J Gastroenterol. 2011;17(10):1373–8.
Koperek O, Aumayr K, Schindl M, Werba G, Soleiman A, Schoppmann S, et al. Phosphorylation of STAT3 correlates with HER2 status, but not with survival in pancreatic ductal adenocarcinoma. APMIS. 2014;122(6):476–81.
Li Z, Zhang D, Zhang H, Miao Z, Tang Y, Sun G, et al. Prediction of peritoneal recurrence by the mRNA level of CEA and MMP-7 in peritoneal lavage of gastric cancer patients. Tumour Biol. 2014;35(4):3463–70.
Sampieri CL, Leon-Cordoba K, Remes-Troche JM. Matrix metalloproteinases and their tissue inhibitors in gastric cancer as molecular markers. J Cancer Res Ther. 2013;9(3):356–63.
Shi M, Liu D, Duan H, Han C, Wei B, Qian L, et al. Catecholamine up-regulates MMP-7 expression by activating AP-1 and STAT3 in gastric cancer. Mol Cancer. 2010;9:269.
Zhao H, Yang Z, Wang X, Zhang X, Wang M, Wang Y, et al. Triptolide inhibits ovarian cancer cell invasion by repression of matrix metalloproteinase 7 and 19 and upregulation of E-cadherin. Exp Mol Med. 2012;44(11):633–41.
Kim H, He Y, Yang I, Zeng Y, Kim Y, Seo YW, et al. delta-Catenin promotes E-cadherin processing and activates beta-catenin-mediated signaling: implications on human prostate cancer progression. Biochim Biophys Acta. 2012;1822(4):509–21.
Yeh YC, Sheu BS, Cheng HC, Wang YL, Yang HB, Wu JJ. Elevated serum matrix metalloproteinase-3 and −7 in H. pylori-related gastric cancer can be biomarkers correlating with a poor survival. Dig Dis Sci. 2010;55(6):1649–57.
Lukaszewicz-Zajac M, Mroczko B, Szmitkowski M. Gastric cancer—the role of matrix metalloproteinases in tumor progression. Clin Chim Acta. 2011;412(19–20):1725–30.
Lee KH, Shin SJ, Kim KO, Kim MK, Hyun MS, Kim TN, et al. Relationship between E-cadherin, matrix metalloproteinase-7 gene expression and clinicopathological features in gastric carcinoma. Oncol Rep. 2006;16(4):823–30.
Zheng HC, Sun JM, Li XH, Yang XF, Zhang YC, Xin Y. Role of PTEN and MMP-7 expression in growth, invasion, metastasis and angiogenesis of gastric carcinoma. Pathol Int. 2003;53(10):659–66.
Panic N, Leoncini E, de Belvis G, Ricciardi W, Boccia S. Evaluation of the endorsement of the preferred reporting items for systematic reviews and meta-analysis (PRISMA) statement on the quality of published systematic review and meta-analyses. PLoS ONE. 2013;8(12):e83138.
Edge SB, Compton CC. The American Joint Committee on Cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol. 2010;17(6):1471–4.
Zintzaras E, Ioannidis JP. HEGESMA: genome search meta-analysis and heterogeneity testing. Bioinformatics. 2005;21(18):3672–3.
Zintzaras E, Ioannidis JP. Heterogeneity testing in meta-analysis of genome searches. Genet Epidemiol. 2005;28(2):123–37.
Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med. 2002;21(11):1539–58.
Song F, Gilbody S. Bias in meta-analysis detected by a simple, graphical test. Increase in studies of publication bias coincided with increasing use of meta-analysis. 471. 1998;316(7129).
Peters JL, Sutton AJ, Jones DR, Abrams KR, Rushton L. Comparison of two methods to detect publication bias in meta-analysis. JAMA. 2006;295(6):676–80.
Gencer S, Sen G, Dogusoy G, Belli AK, Paksoy M. Yazicioglu MB beta-catenin-independent noncanonical Wnt pathway might be induced in gastric cancers Turk. J Gastroenterol. 2010;21(3):224–30.
Kuang RG, Wu HX, Hao GX, Wang JW, Zhou CJ. Expression and significance of IGF-2, PCNA, MMP-7, and alpha-actin in gastric carcinoma with Lauren classification. Turk J Gastroenterol. 2013;24(2):99–108.
Senota A, Itoh F, Yamamoto H, Adachi Y, Hinoda Y, Imai K. Relation of matrilysin messenger RNA expression with invasive activity in human gastric cancer. Clin Exp Metastasis. 1998;16(4):313–21.
Sentani K, Matsuda M, Oue N, Uraoka N, Naito Y, Sakamoto N, et al. Clinicopathological significance of MMP-7, laminin gamma2 and EGFR expression at the invasive front of gastric carcinoma. Gastric Cancer. 2013
Yonemura Y, Fujimura T, Ninomiya I, Kim BS, Bandou E, Sawa T, et al. Prediction of peritoneal micrometastasis by peritoneal lavaged cytology and reverse transcriptase-polymerase chain reaction for matrix metalloproteinase-7 mRNA. Clin Cancer Res. 2001;7(6):1647–53.
Luo M, Wang XJ, Yang FF. The correlation between the expression of matrix metalloproteinase-7 and the lymph node micrometastases in gastric carcinoma. J Clin Surg. 2013;21(4):269–70.
Dong RK, Zhang D, Huang JP, Han MF, Wang QB, Fu J, et al. Expression and relationship between matrix metalloproteinase-7 and E-cadherin in gastric cancer. Cancer Res Clin. 2011;23(1):25–7.
Guo SJ, Li YY, Lv JL, Wang FC. Relationship between matrix metalloproteinase-7 mRNA expression and pathological characteristic in gastric carcinoma. J Chin Oncol. 2005;11(1):31–2.
Xiang HP, Zhang CL. Expression of MMP-7 gene in gastric cancer tissues and its correlation with metastasis in portal vein nlood and peritoneal cavity. Anhui Med J. 2007;28(3):176–9.
Hua H, Li M, Luo T, Yin Y, Jiang Y. Matrix metalloproteinases in tumorigenesis: an evolving paradigm. Cell Mol Life Sci. 2011;68(23):3853–68.
Shuman Moss LA, Jensen-Taubman S, Stetler-Stevenson WG. Matrix metalloproteinases: changing roles in tumor progression and metastasis. Am J Pathol. 2012;181(6):1895–9.
Ii M, Yamamoto H, Adachi Y, Maruyama Y, Shinomura Y. Role of matrix metalloproteinase-7 (matrilysin) in human cancer invasion, apoptosis, growth, and angiogenesis. Exp Biol Med (Maywood). 2006;231(1):20–7.
Duffy MJ, McGowan PM, Gallagher WM. Cancer invasion and metastasis: changing views. J Pathol. 2008;214(3):283–93.
Yasui W, Oue N, Aung PP, Matsumura S, Shutoh M, Nakayama H. Molecular-pathological prognostic factors of gastric cancer: a review. Gastric Cancer. 2005;8(2):86–94.
Acknowledgments
We would like to acknowledge the reviewers for their helpful comments on this paper.
Conflict of interest
None
Author information
Authors and Affiliations
Corresponding author
Additional information
Zi-Wen Long and Jiang-Li Wang are co-first authors.
Rights and permissions
About this article
Cite this article
Long, ZW., Wang, JL. & Wang, YN. Matrix metalloproteinase-7 mRNA and protein expression in gastric carcinoma: a meta-analysis. Tumor Biol. 35, 11415–11426 (2014). https://doi.org/10.1007/s13277-014-2441-8
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s13277-014-2441-8