In silico analysis and validation of the proliferative potential of CLDN1 expression in gastric cancer

Tight junction protein claudin-1 (CLDN1) is mainly involved in the intercellular barrier function of epithelial cells and is known to be dysregulated in many cancer types, including gastrointestinal cancers. However, the mechanisms behind their potential involvement in the proliferation and survival of tumor cells remain unexplored. In this study we sought to investigate the potential role and possible regulators of CLDN1 in gastric cancer. By analyzing the gastric tumors from publicly available genome-wide messenger RNA expression profiles, CLDN1 was identified to be overexpressed in gastric tumors when compared with normal gastric tissues. Association between CLDN1 expression and clinical molecular subtype characteristics of gastric cancer showed an elevated CLDN1 expression pattern in intestinal and proliferative types of gastric cancer. Using in vitro CLDN1 perturbation analysis in gastric cancer cell lines, we confirmed the potential role of CLDN1 in cellular proliferation. Aided by the integrative analysis of the pathway prediction method with CLDN1 expression in gastric tumors, we demonstrated the negative association between estrogen-α and CLDN1 expression in gastric tumors. Our results highlight the potential involvement of CLDN1 expression in gastric cancer.