Epigenetic Downregulation and Growth Inhibition of IGFBP7 in Gastric Cancer

Background: Insulin-like growth factor-binding protein 7 (IGFBP7) has been found to be a tumor suppressor in several human cancers, but the role of IGFBP7 in gastric cancer has not yet been fully investigated. Herein, we examined the epigenetic downregulation of IGFBP7 expression in gastric cancer. Methods: Expression and methylation of IGFBP7 in gastric cancer cells and primary gastric cancer patients were determined using qRT-PCR, western blot, immunohistochemistry, and methylation specific-PCR, respectively. The effects of IGFBP7 on gastric cancer cells were investigated by various experimental conditions, such as proliferation, colony formation, apoptosis, invasion, and migration assay. Results: IGFBP7 methylation was inversely correlated with IGFBP7 expression in gastric cancer. Univariate and multivariate analysis showed that IGFBP7 expression and tumor stage were independent prognostic factors. IGFBP7 knockdown increased gastric cancer cell growth, invasion, and migration, whereas IGFBP7 overexpression in gastric cancer cells induced cell growth inhibition and apoptosis. Conclusion: Our data suggest that IGFBP7 functions as a tumor suppressor in gastric cancer via an epigenetic pathway.