Abstract
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. Twist and MMP-9 expression in tissue sections of 37 gastric carcinomas was evaluated with immunohistochemistry. The staining results were compared with clinicopathologic features and to patients'outcome. 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). 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.
Highlights
Gastric cancer is the second most lethal cancer with approximately 800,000 deaths each year in the world (Jemal et al, 2011)
In the process of tumor invasion and metastasis, cancer cells obtain the phenotype and invasive characteristics of mesenchymal cells through Epithelial-mesenchymal transition (EMT) to achieve the infiltration of surrounding tissue
In the process of tumor metastasis, cancer cells lose their polarity and intercellular adhesions and acquire the phenotype and invasive characteristics of mesenchymal cells through EMT to achieve the infiltration of surrounding tissue (Sanchez-Tillo et al, 2012)
Summary
Gastric cancer is the second most lethal cancer with approximately 800,000 deaths each year in the world (Jemal et al, 2011). Epithelial-mesenchymal transition (EMT) is one of the critical events in such multistep process, a developmental process characterized by loss of epithelial markers, gain of mesenchymal markers and changes in cellular morphology and phenotype (Hugo et al, 2007; Yang et al, 2008). In this process, the adhesion structures between epithelial cells gradually disappear and cell-cell adhesion decreases; in addition, changes occur in cell polarity and the cytoskeleton (Lee et al, 2006; Thiery et al, 2009). Recent researches indicated that the abnormal EMT is closely associated with epithelial tumors, such as breast cancer (Zhang et al, 2012), lung cancer (Nagathihalli et al, 2012), colon carcinoma (Bellovin et al, 2005), prostate cancer (Shiota et al, 2012), cervical cancer (Lei et al, 2012), and gastric cancer (Jia et al, 2013)
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