High expression of GMⅡ is associated with poor prognosis of gastric cancer patients

Background: Being an important N-glycosylation enzyme in eukaryotic cells, Golgi α-mannosidaseⅡ (GMⅡ) has been suggested to function as a target for cancer treatment based on the inhibitory effect on cancer growth and metastasis by the swainsonine, an inhibitor of GMⅡ. This study aims to investigate GMⅡ expression and its prognostic value in primary gastric cancer. Methods: The GMⅡ expression was examined by using the quantitative PCR and Western blotting in 37 paired gastric cancer and noncancerous tissues. We analyzed the relationship between its expression and the clinicopathological parameters by immunohistochemistry in 185 paraffin-embedded gastric cancer tissue specimens. Furthermore, we detected the GMⅡ expression in cultured gastric cancer cell lines and the normal gastric cell line and observed the changes of proliferative and invasive capacities of gastric cell lines after GMⅡ scilencing and overexpressing in vitro. Results: The GMⅡ mRNA (P<0.0001) and protein (P<0.01) expression of 37 tumor tissues were increased compared with those of the matched adjacent normal tissues. Human gastric cancer cell lines also showed higher GMⅡ expression (P<0.001) compared with normal gastric cell lines. The immunohistochemical analysis revealed that GMⅡ was an independent predictor of the overall survival of patients. In addition, GMⅡ overexpression in the normal gastric cell line GES-1 significantly promoted the cell proliferation and invasion, while GMⅡ knockdown in gastric cancer cell line BGC-823 significantly inhibited the cell proliferation and invasion. Conclusion: GMⅡ may become an indicator for monitoring the prognosis of primary gastric cancer and it may provide a new direction for precise treatment.