Combined epithelial-mesenchymal transition with cancer stem cell-like marker as predictors of recurrence after radical resection for gastric cancer

BACKGROUND: The aim of the study was to identify the incidence and the predictors of recurrence after curative resection and the clinical significance of epithelial-mesenchymal transition (EMT) and stem cell-like phenotypes in gastric cancer. METHODS: In a total of 1,463 patients that underwent curative resection for gastric cancer between January 2001 and January 2008 at Drum Tower Hospital, 402 (27.5%) experienced recurrence. They were divided into early recurrence (within two years) and late recurrence (more than two years). The clinicopathological characteristics, including five EMT-related proteins (Snail-1, ZEB-1, E-cadherin, vimentin, and β-catenin) and the gastric cancer stem cell markers CD44 and CD54, therapeutic modalities, survival time after recurrence, and recurrence patterns were compared between the two groups. RESULTS: Loss of E-cadherin expression and aberrant expression of vimentin and the known gastric cancer stem cell maker CD44 were significantly associated with aggressive clinicopathologic features. Multivariate analysis showed that stage III gastric cancer patients with early recurrence had larger tumors and more lymph node metastasis, coupled with aberrant expression EMT and cancer stem cell marker, than patients with late recurrence. Early recurrence was associated with more distant metastasis than late recurrence and patients tended to die within two years of recurrence. CONCLUSIONS: Combined EMT with cancer stem cell-like marker is a predictor of recurrence after radical resection for gastric cancer. Advanced TNM stage was associated with early cancer death after recurrence.