Abstract
BackgroundThe 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.MethodsIn 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.ResultsLoss 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.ConclusionsCombined 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.
Highlights
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
Expression of epithelial-mesenchymal transition and cancer stem cell-like marker association with tumor recurrence Table 1 shows the clinicopathologic characteristics of the patients with early recurrence and late recurrence
Among the perioperative variables recorded for univariate analysis were: presence of Cluster of differentiation 44 (CD44), Cluster of differentiation 54 (CD54), and vimentin, loss of E-cadherin and β-catenin expression, with a tumor size of 5 cm or more, more advanced T-stage, and a more advanced TNM stage with early recurrence to late recurrence Multivariate analysis was employed to identify the independent risk factors for overall recurrence
Summary
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. CD44positive tumor cells were shown to have cancer stem cell properties, including the tumor-initiating ability [2], and Chen et al [3] showed that CD44 + CD54+ cells exhibit cancer stem cell capabilities in gastric cancer tissues. These tumor-initiating cells provide a reservoir that can cause tumor recurrence after therapy [4]
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