V-set and immunoglobulin domain containing 1 (VSIG1) as an emerging target for epithelial–mesenchymal transition of gastric cancer

V-set and Immunoglobulin domain containing 1 (VSIG1) is a cell–cell adhesion molecule which role in the genesis and evolution of gastric cancer (GC) is not understood. Only three Medline-indexed papers have focused on the role of VSIG1 in GC. The clinicopathological features of 94 GCs were examined in association with immunohistochemical (IHC) patterns of VSIG1, E-cadherin, and β-catenin which were assessed in the tumor core (central) vs. invasive edge. Cases were classified depending on the VSIG1 expression: membrane/membrane in both core and invasive front; null/negative staining in both core and invasive front; and cases with translocational patterns: membrane core/cytoplasmic buds and cytoplasmic core/null buds. Most of the tumors showed null pattern (n = 54). Cases with translocational patterns (n = 20) were GCs with a high lymph node ratio value (≥ 0.26) and advanced Dukes-MAC-like stage. Of the 20 total cases, 9 showed membrane-to-nuclear translocation of β-catenin and loss of E-cadherin, as indicators of epithelial–mesenchymal transition. All cases with membrane/membrane pattern (n = 20) involved the distal stomach. The poorest overall survival was registered in patients with subcellular translocation of VSIG1, compared to those with either membrane/membrane or null patterns (p = 0.002). In GC, VSIG1 acts as an adhesion membrane protein but its membrane-cytoplasmic translocation can be an indicator of epithelial–mesenchymal transition due to cytoplasmic VSIG1-mediated activation of canonical Wnt/β-catenin signaling pathway.