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http://dx.doi.org/10.7314/APJCP.2013.14.9.5055

Overexpression of Twist and Matrix Metalloproteinase-9 with Metastasis and Prognosis in Gastric Cancer  

Gao, Xing-Hui (Department of Laboratory Medicine & Center for Gene Diagnosis, Zhongnan Hospital of Wuhan University)
Yang, Xue-Qin (Medical School of Jingchu University of Technology)
Wang, Bi-Cheng (Department of Laboratory Medicine & Center for Gene Diagnosis, Zhongnan Hospital of Wuhan University)
Liu, Shao-Ping (Hubei Key Laboratory of Tumor Biological Behaviors & Hubei Cancer Clinical Study Center)
Wang, Fu-Bing (Department of Laboratory Medicine & Center for Gene Diagnosis, Zhongnan Hospital of Wuhan University)
Publication Information
Asian Pacific Journal of Cancer Prevention / v.14, no.9, 2013 , pp. 5055-5060 More about this Journal
Abstract
Objective: Twist, a basic helix-loop-helix transcription factor, plays a key role in the metastatic progression of human cancer. Matrix metalloproteinase (MMP)-9 is an endopeptidase that digests basement membrane type IV collagen, therefore being possibly related to tumor progression. It has been reported that Twist and matrix metalloproteinase-9 (MMP-9) are expressed in gastric cancers. However, the exact roles of Twist and MMP-9 in tumor metastasis and prognosis remain unclear. The aim of this study was to casts light on this question. Methods:Twist and MMP-9 expression in tissue sections of 37 gastric carcinomas was evaluated with immunohistochemistry. The staining results were compared with clinicopatholgic features and to patients' outcome. Results: Twist positive expression was significantly increased in gastric cancer cases with lymph node metastasis (P=0.023). But no correlations were found between MMP-9 overexpression and clinicopathologic features, such as recurrence, TNM stage, and lymph node metastasis. Overall survival (OS) was significantly correlated with recurrence, serosa invasion, TNM stages, distant metastasis, and MMP-9 (P=0.027, 0.021, 0.000, 0.024 and 0.036, respectively). Disease-free survival (DFS) was prominently related to recurrence location, serosa invasion and TNM stages (P=0.000, 0.038 and 0.003, respectively). In the Cox regression multivariate analysis, TNM stage, distant metastasis and MMP-9 were significantly associated with prognosis of gastric cancer (P=0.002, 0.019, and 0.032, respectively). Conclusions: This study showed Twist positive expression to be significantly correlated with lymph node metastasis in gastric cancer. MMP-9 overexpression is associated with OS, suggesting that MMP-9 is a prognostic indicator for survival in patients with gastric cancer.
Keywords
Gastric cancer; twist; matrix metalloproteinase-9; prognosis; survival;
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1 Fidler IJ (2003). The pathogenesis of cancer metastasis: the 'seed and soil' hypothesis revisited. Nat Rev Cancer, 3, 453-8.   DOI   ScienceOn
2 Bellovin DI, Bates RC, Muzikansky A, et al (2005). Altered localization of p120 catenin during epithelial to mesenchymal transition of colon carcinoma is prognostic for aggressive disease. Cancer Res, 65, 10938-45.   DOI   ScienceOn
3 Christofori G (2006). New signals from the invasive front. Nature, 441, 444-50.   DOI   ScienceOn
4 Egeblad M, Werb Z. (2002). New functions for the matrix metalloproteinases in cancer progression. Nat Rev Cancer, 2, 161-74.   DOI   ScienceOn
5 Gupta GP, Massague J (2006). Cancer metastasis: building a framework. Cell, 127, 679-95.   DOI   ScienceOn
6 Hoek K,Rimm DL, Williams KR, et al (2004). Expression profiling reveals novel pathways in the transformation of melanocytes to melanomas. Cancer Res, 64, 5270-82.   DOI   ScienceOn
7 Hugo H, Ackland ML, Blick T, et al (2007). Epithelial-- mesenchymal and mesenchymal--epithelial transitions in carcinoma progression. J Cell Physiol, 213, 374-83.   DOI   ScienceOn
8 Hui L, Zhang S, Dong X, et al (2013). Prognostic significance of twist and N-cadherin expression in NSCLC. PLoS One, 8, e62171.   DOI
9 Jemal A, Bray F, Center MM, et al (2011). Global cancer statistics. CA Cancer J Clin, 61, 69-90.   DOI
10 Lee JM, Dedhar S, Kalluri R, et al (2006). The epithelialmesenchymal transition: new insights in signaling, development, and disease. J Cell Biol, 172, 973-81.   DOI   ScienceOn
11 Jia L, Wu J, Zhang L (2013). Restoration of miR-1228* expression suppresses epithelial-mesenchymal transition in gastric cancer. PLoS One, 8, e58637.   DOI
12 Kang Y, Massague J (2004). Epithelial-mesenchymal transitions: twist in development and metastasis. Cell, 118, 277-9.   DOI   ScienceOn
13 Ke P, Wu ZD, Wen HS,et al(2013). Current Evidence on Associations Between the MMP-7 (-181A>G) Polymorphism and Digestive System Cancer Risk. Asian Pac J Cancer Prev, 14, 2269-72.   DOI   ScienceOn
14 Lee TK, Poon RT, Yuen AP et al (2006). Twist overexpression correlates with hepatocellular carcinoma metastasis through induction of epithelial-mesenchymal transition. Clin Cancer Res, 12, 5369-76.   DOI   ScienceOn
15 Lei C, Wang Y, Huang Y, et al (2012). Up-regulated miR155 reverses the epithelial-mesenchymal transition induced by EGF and increases chemo-sensitivity to cisplatin in human Caski cervical cancer cells. PLoS One, 7, e52310.   DOI
16 Lin CY, Tsai PH, Kandaswami CC, et al (2011). Matrix metalloproteinase-9 cooperates with transcription factor Snail to induce epithelial-mesenchymal transition. Cancer Sci, 102, 815-27.   DOI   ScienceOn
17 Martin TA, Goyal A, Watkins G, et al (2005). Expression of the transcription factors snail, slug, and twist and their clinical significance in human breast cancer. Ann Surg Oncol, 12, 488-96.   DOI
18 Mehlen P, Puisieux A (2006). Metastasis: a question of life or death. Nat Rev Cancer, 6, 449-58.   DOI   ScienceOn
19 Nagase H, Woessner JJ (1999). Matrix metalloproteinases. J Biol Chem, 274, 21491-4.   DOI
20 Nagathihalli NS, Massion PP, Gonzalez AL, et al (2012). Smoking induces epithelial-to-mesenchymal transition in non-small cell lung cancer through HDAC-mediated downregulation of E-cadherin. Mol Cancer Ther, 11, 2362-72.   DOI
21 Ruokolainen H, Paakko P, Turpeenniemi-Hujanen T (2004). Expression of matrix metalloproteinase-9 in head and neck squamous cell carcinoma: a potential marker for prognosis. Clin Cancer Res, 10, 3110-6.   DOI   ScienceOn
22 Stamenkovic I (2000). Matrix metalloproteinases in tumor invasion and metastasis. Semin Cancer Biol, 10, 415-33.   DOI   ScienceOn
23 Sanchez-Tillo E, Liu Y, de Barrios O, et al (2012). EMTactivating transcription factors in cancer: beyond EMT and tumor invasiveness. Cell Mol Life Sci, 69, 3429-56.   DOI   ScienceOn
24 Shiota M, Zardan A, Takeuchi A, et al(2012). Clusterin mediates TGF-beta-induced epithelial-mesenchymal transition and metastasis via Twist1 in prostate cancer cells. Cancer Res, 72, 5261-72.   DOI
25 Sillanpaa S, Anttila M, Voutilainen K, et al(2007). Prognostic significance of matrix metalloproteinase-9 (MMP-9) in epithelial ovarian cancer. Gynecol Oncol, 104, 296-303.   DOI   ScienceOn
26 Steeg PS (2006). Tumor metastasis: mechanistic insights and clinical challenges. Nat Med, 12 , 895-904.   DOI   ScienceOn
27 Thiery JP (2002). Epithelial-mesenchymal transitions in tumour progression. Nat Rev Cancer, 2 , 442-54.   DOI   ScienceOn
28 Weigelt B, Peterse JL, van 't Veer LJ (2005). Breast cancer metastasis: markers and models. Nat Rev Cancer, 5, 591-602.   DOI   ScienceOn
29 Thiery JP, Acloque H, Huang RY, et al (2009). Epithelialmesenchymal transitions in development and disease. Cell, 139, 871-90.   DOI   ScienceOn
30 Thiery JP, Sleeman JP(2006). Complex networks orchestrate epithelial-mesenchymal transitions. Nat Rev Mol Cell Biol, 7, 131-42.   DOI   ScienceOn
31 Thisse B, el Messal M, Perrin-Schmitt F (1987). The twist gene: isolation of a Drosophila zygotic gene necessary for the establishment of dorsoventral pattern. Nucleic Acids Res, 15, 3439-53.   DOI
32 Yan-Qi Z, Xue-Yan G, Shuang H, et al (2007). Expression and significance of TWIST basic helix-loop-helix protein overexpression in gastric cancer. Pathology, 39, 470-5.   DOI   ScienceOn
33 Wu ZS, Wu Q, Yang JH (2008). Prognostic significance of MMP-9 and TIMP-1 serum and tissue expression in breast cancer. Int J Cancer, 122, 2050-6.   DOI   ScienceOn
34 Yang J, Weinberg RA (2008). Epithelial-mesenchymal transition: at the crossroads of development and tumor metastasis. Dev Cell, 14, 818-29.   DOI   ScienceOn
35 Yang J, Mani SA, Donaher JL, et al (2004). Twist, a master regulator of morphogenesis, plays an essential role in tumor metastasis. Cell, 117, 927-39.   DOI   ScienceOn
36 Yoo YA, Kang MH, Lee HJ, et al (2011). Sonic hedgehog pathway promotes metastasis and lymphangiogenesis via activation of Akt, EMT, and MMP-9 pathway in gastric cancer. Cancer Res, 71, 7061-70.   DOI   ScienceOn
37 Yoshida J, Horiuchi A, Kikuchi N, et al (2009). Changes in the expression of E-cadherin repressors, Snail, Slug, SIP1, and Twist, in the development and progression of ovarian carcinoma: the important role of Snail in ovarian tumorigenesis and progression. Med Mol Morphol, 42, 82-91.   DOI
38 Zhao XL, Sun T, Che N, et al (2011). Promotion of hepatocellular carcinoma metastasis through matrix metalloproteinase activation by epithelial-mesenchymal transition regulator Twist1. J Cell Mol Med, 15, 691-700.   DOI   ScienceOn
39 Yu Q, Zhang K, Wang X, et al (2010). Expression of transcription factors snail, slug, and twist in human bladder carcinoma. J Exp Clin Cancer Res, 29, 119.   DOI   ScienceOn
40 Zhang J, Liang Q, Lei Y, et al (2012). SOX4 induces epithelialmesenchymal transition and contributes to breast cancer progression. Cancer Res, 72, 4597-608.   DOI
41 Radisky ES, Radisky DC (2010). Matrix metalloproteinaseinduced epithelial-mesenchymal transition in breast cancer. J Mammary Gland Biol Neoplasia, 1, 201-12.
42 Zhang K, Chen D, Jiao X, et al (2011). Slug enhances invasion ability of pancreatic cancer cells through upregulation of matrix metalloproteinase-9 and actin cytoskeleton remodeling. Lab Invest, 91, 426-38.   DOI   ScienceOn
43 Sampieri CL, de la Pena S, Ochoa-Lara M, et al (2010). Expression of matrix metalloproteinases 2 and 9 in human gastric cancer and superficial gastritis. World J Gastroenterol, 16, 1500-5.   DOI