Overexpression of Endothelial Cell Specific Molecule-1 (ESM-1) in Gastric Cancer

Abstract

The endothelial cell-specific molecule-1 (ESM-1) gene is involved in various biological events. This study was designed to clarify its clinical significance and explore its biological behavior in gastric cancer (GC). ESM-1 mRNA expression was evaluated by real-time PCR in GC (n=34) and matched adjacent normal tissues (n=14). The expression of ESM-1 protein was investigated by immunohistochemistry in GC (n=159) and matched normal tissues (n=40), and its correlation with the clinicopathological features and overall survival of patients was analyzed. Microvessel density (MVD) in GC was assessed by anti-CD34 and the pattern of ESM-1 expression in tumor-related vascular was evaluated. The effect of ESM-1 promotion of proliferation in the GC MKN28 cell line and human microvascular endothelial cell line HMEC-1 were tested using the MTT assay. ESM-1 mRNA was significantly overexpressed in GC compared with adjacent noncarcinoma controls (P<0.01). ESM-1 protein was predominantly expressed in GC. ESM-1 expression was associated with distant metastasis and Borrmann type IV (P<0.05) and was strongly associated with vascular invasion (P=0.0057). Patients with ESM-1 expression showed lower 5-year survival rate (P=0.0339). Multivariate analysis revealed that ESM-1 was an independent prognostic factor. In GC, CD34-MVD of GC vessels positively expressing ESM-1 was higher than that of GC with negative vessels expression of ESM-1 (P<0.05). Besides, ESM-1 antibody dose-dependently impaired MKN28 and HMEC-1 growth. ESM-1 is overexpressed in GC and can serve as a tumor biomarker to predict survival of GC patients, and it might promote tumor angiogenesis and growth in GC and, hence, may represent a potential therapeutic target.