Androgens as potential prognostic biomarkers are correlated with E-cadherin/β-catenin pathway in endometrial carcinoma

Abstract

Background Androgens are associated with the risk of endometrial carcinoma (EC). However, their roles as prognostic factors are less clear. This study aimed to investigate the prognostic impact of different androgenic hormones and further uncovered the involved mechanism. Methods We examined associations between endogenous testosterone levels (total, bioavailable and free testosterone) and the clinical outcomes in patients with EC. The biological function of androgen was examined by in vitro and in vivo experiments. Results Compared with healthy controls, patients with EC showed significantly higher levels of testosterone. However, higher levels of bioavailable and free testosterone in EC patients correlated with favourable clinicopathological features. Kaplan-Meier survival analysis indicated that higher bioavailable and free testosterone levels were associated with better overall survival (P = 0.048, P = 0.036, respectively), which was not observed in subgroup analysis of total testosterone (P = 0.097). Furthermore, in vitro and in vivo experiments confirmed that androgen-dihydrotestosterone (DHT) could inhibit the migration and invasion of EC cells. Mechanistically, DHT could recruit β-catenin to E-cadherin to stabilize the adhesion junctions and inhibit β-catenin translocation into the nucleus in EC cells. Conclusions Androgens may potentially predict the prognosis of patients with EC.