Overexpression of Transmembrane Protein BST2 is Associated with Poor Survival of Patients with Esophageal, Gastric, or Colorectal Cancer.

Abstract

Gastrointestinal (GI) cancer, including gastric cancer (GC), colorectal cancer (CRC), and esophageal squamous cell carcinoma (ESCC), is the most common malignancy worldwide. To identify genes that encode transmembrane proteins present in GI cancer, Escherichia coli ampicillin secretion trap libraries were generated from MKN-74 GC cells, and BST2 was identified as overexpressed in GC. This study analyzed the expression and function of the BST2 gene in human GI cancers and examined the relationship between bone marrow stromal antigen-2 (BST-2) expression and GI patient clinicopathologic characteristics. Expression and distribution of BST-2 protein was analyzed by immunohistochemistry in 180 GC cases, 140 CRC cases, and 132 ESCC cases. Cell growth was analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Immunohistochemical analysis of BST-2 in GC tissues showed that 65 (36%) of 180 GC cases were positive for BST-2. Uni- and multivariate analyses demonstrated that BST-2 expression is an independent prognostic classifier of GC patients. Immunohistochemical analysis showed that 46% of 140 CRC cases and 27% of 132 ESCC cases were positive for BST-2. In ESCC, BST-2 expression was an independent prognostic predictor for survival. The growth of BST2 small interfering RNA (siRNA)-transfected GC cells was significantly slower than the growth of negative control siRNA-transfected GC cells. The levels of phosphorylated epidermal growth factor receptor, extracellular signal-regulated kinase, and Akt were lower in BST2 siRNA-transfected GC cells than in control cells. The results suggest that BST-2 is involved in tumor progression and serves as an independent prognostic classifier for patients with GC. Because BST-2 is expressed on the cell membrane, BST-2 could be a therapeutic target for GC, CRC, and ESCC.