High expression of GM II is associated with poor prognosis of gastric cancer patients

Abstract

Background: Being an important N-glycosylation enzyme in eukaryotic cells, Golgi α- mannosidase II (GM II) 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 GM II. This study aims to investigate GM II expression and its prognostic value in primary gastric cancer. Methods: The GM II 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 GM II 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 GM II scilencing and overexpressing in vitro. Results: The GM II 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 GM II expression (P<0.001) compared with normal gastric cell lines. The immunohistochemical analysis revealed that GM II was an independent predictor of the overall survival of patients. In addition, GM II overexpression in the normal gastric cell line GES-1 significantly promoted the cell proliferation and invasion, while GM II knockdown in gastric cancer cell line BGC-823 significantly inhibited the cell proliferation and invasion. Conclusion: GM II may become an indicator for monitoring the prognosis of primary gastric cancer and it may provide a new direction for precise treatment.