Significance and expression of metdherin in gastric adenocarcinoma and its regulating mechanism of invasion and migration

Objective This study aimed at observing expression and clinical significance of metadherin in gastric adenocarcinoma and exploring the potentially regulating mechanism of metadherin in invation and migration of gastric cancer. Methods Expressions of metadherin and E-cadherin in primary lesion of gastric cancer were detected by immunohistochemistry and their correlation to clinicopathologic characteristics and prognosis were analyzed by Chi-square tests. Transwell assay and wound healing assay were applied for the ability of invasion and metastasis in gastric cancer cells. Then, the down-regulatied metadherin expression in MKN45 cells by RNA interference (siRNA) was carried out and furthermore, the regulation role of metadherin in epithelial-mesenchymal transition was analyzed also in invasion and migration of gastric cancer cells. Results The positive expression of metadherin was correlated to invading depth (P=0.029), lymph node metastasis (P=0.001), TNM stage (P=0.014) and inhibiting E-cadherin expression (P=0.001). The patients with positive metabherin shared poorer prognosis. Furthermore, the down-regulated metabherin in MKN45 cells would result in the increasing expression of E-cadherin, as well as decreasing expression of N-cadherin, Slug and Snail. At the same time, the abilities of invasion (P=0.027) and migration (P=0.008) of MKN45 cells was decreased. Conclusion metabherin induces EMT in metastasis of gastric adenocarcinoma via activating either Slug or Snail but not twist, which would result in the poorer prognosis. Key words: MTDH; Stomach neoplasms; Epithelial-mesenchymal transition; Metastasis; Prognosis; Chi-Square distribution