Evaluation of Slug expression is useful for predicting lymph node metastasis and survival in patients with gastric cancer

Abstract

BackgroundSlug is a transcription factor that activates the epithelial–mesenchymal transition (EMT) process in cancer progression. The aim of our study was to evaluate the clinical significance of Slug expression in gastric cancer.MethodsThe expression of Slug in gastric cancer tissues of 456 patients who underwent gastrectomy was evaluated by immunohistochemistry using tissue microarrays. Slug expression level was defined by the composite score determined by multiplying the tumor staining scores for intensity and extent. The associations of Slug expression with clinicopathological characteristics and overall and recurrence-free survival were analyzed.ResultsPatients were divided into three groups according to Slug composite score (≤4, 6, and 9). Low, mid, and high expression of Slug was observed in 104 (22.7%), 130 (28.3%), and 225 (49.0%) of cases, respectively. Overall survival and recurrence-free survival progressively increased from high to low Slug expression. In terms of lymph node metastasis, the rate of positive lymph node metastasis was 38/104 (36.5%), 79/130 (60.8%), and 178/225 (79.1%) in low, mid, and high Slug expression groups, respectively, displaying a tendency to increase with higher Slug expression. In a multivariate analysis adjusting for patient age, tumor size, tumor depth, and histology, high Slug expression was associated with a high rate of positive lymph node metastasis compared with low Slug expression (odds ratio 3.42; 95% confidence interval, 1.74–6.69). In a subgroup analysis of T1 cancer, patients with negative Slug expression (defined as <5% positive tumor cells or no/weak staining) showed no lymph node metastasis (0/13), whereas those with positive Slug expression showed 15.9% (17/107) lymph node metastasis, with a negative predictive value of 100%.ConclusionsHigh expression of Slug in gastric cancer tissue was associated with lymph node metastasis and poor survival. Evaluation of Slug would be useful for discriminating patients at high risk of lymph node metastasis in early gastric cancer.