Anterior gradient 2 is overexpressed in extramammary Paget's disease and involved in cell survival

Background Extramammary Paget's disease (EMPD) is a rare skin cancer whose etiology and pathogenesis remain unclear. Because of limited treatment options, patients with advanced stages have a poor prognosis; therefore, identifying novel biomarkers for early detection and evaluation of therapeutic efficacy is necessary. Objective To investigate the association between anterior gradient 2 (AGR2) expression and clinical features in patients with EMPD and the potential involvement of AGR2 in the pathogenesis of EMPD. Methods Sixty-two tissue samples and 60 serum samples were evaluated using immunohistochemistry and enzyme-linked immunosorbent assay. In vitro experiments were performed using the EMPD cell line, KS-EMPD-1, to assess the effects of silencing AGR2 on cell growth, invasion, and migration. Results Patients with AGR2 overexpression in tumor tissues tended to have a poor prognosis; however, the difference was not statistically significant. Serum AGR2 concentrations were significantly higher in patients with EMPD with or without metastasis than in healthy controls and decreased after treatment. AGR2 knockdown decreased cell number and induced apoptosis in EMPD cells, suggesting that AGR2 may influence the viability of EMPD cells via apoptosis. Conclusion AGR2 is overexpressed in patients with EMPD and plays an important role in the pathogenesis of EMPD.