The influence of transforming growth factor-α, cyclooxygenase-2, matrix metalloproteinase (MMP)-7, MMP-9 and CXCR4 proteins involved in epithelial-mesenchymal transition on overall survival of patients with gastric cancer.

ABSTRACT

AIMS: Determination of prognostic parameters that are predictive of survival of gastric cancer (GC) may allow better identification of patients who could benefit from current chemotherapy regimens. To assess the correlation between tumour progression and epithelial-mesenchymal transition (EMT), we assayed the expression levels of selected molecules involved in EMT [CD44, transforming growth factor (TGF)-α, cyclooxygenase-2 (COX-2), matrix metalloproteinase (MMP)-7, MMP-9 and C-X-C chemokine receptor (CXCR4)], and correlated these with overall patient survival (OS) and disease stage. METHODS AND RESULTS: Medical records and pathological biopsy results of 137 patients with GC were evaluated retrospectively. Spearman's correlation analysis showed that expression of CXCR4 was correlated significantly with the expression of all other proteins studied. In contrast, COX-2 expression correlated significantly with the expression of only MMP-7 (P = 0.011), MMP-9 (P = 0.015) and CXCR4 (P = 0.013). We observed significant negative correlations between OS and the expression of TGF-α (P = 0.017), COX-2 (P < 0.001), CXCR4 (P = 0.010), MMP-7 (P = 0.020) and MMP-9 (P = 0.015). On multivariate analysis, only COX-2 was an independent prognostic factor for OS [hazard ratio (HR) = 3.34; 95% confidence interval (CI) 1.43-9.75; P = 0.002). CONCLUSIONS: COX-2, TGF-α, MMP-7, MMP-9 and CXCR4 are associated with poor OS in gastric cancer.