Aberrant Expression of the Autocrine Motility Factor Receptor Correlates with Poor Prognosis and Promotes Metastasis in Gastric Carcinoma

AMFR, autocrine motility factor receptor, also called gp78, is a cell surface cytokine receptor which has a dualrole as an E3 ubiquitin ligase in endoplasmic reticulum-associated degradation. AMFR expression is associatedwith tumor malignancy. We here investigated the clinical significance of AMFR and its role in metastasis andprognosis in gastric cancer. Expression of AMFR, E-cadherin and N-cadherin in cancer tissues and matchedadjacent normal tissues from 122 gastric cancer (GC) patients undergoing surgical resection was assessed byimmunohistochemistry. Levels of these molecules in 17 cases selected randomly were also analysed by Westernblotting. AMFR expression was significantly increased in gastric cancer tissues, and associated with invasiondepth and lymph node metastasis. Kaplan-Meier analysis showed AMFR expression correlated with poor overallsurvival and an increased risk of recurrence in the GC cases. Cox regression analysis suggested AMFR to bean independent predictor for overall and recurrence-free survival. E-cadherin expression was decreased ingastric cancer tissues; conversely, N-cadherin was increased. Expression of AMFR negatively correlated withE-cadherin expression, whereas N-cadherin expression showed a significant positive correlation with AMFRexpression. AMFR might be involved in the regulation of epithelial-mesenchymal transition, with aberrantexpression correlating with a poor prognosis and promoting invasion and metastasis in GCs.