Prognostic significance of the level of serum osteoprotegerin in patients with bladder cancer

Abstract

4581 Background: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) plays an important role in cytotoxic T lymphocyte-mediated and natural killer cell-mediated apoptosis against cancer cells. Since Osteoprotegerin (OPG) is a soluble decoy receptor for TRAIL, circulating OPG has been implicated in protection from TRAIL-mediated apoptosis. This possibility was examined in patients with bladder cancer. Methods: Serum OPG levels of 185 patients with bladder cancer were determined by using an enzyme-linked immunosorbent assay. Anti-autologous tumor cytotoxic activity of peripheral blood lymphocytes was assessed by the 12-h Cr release assay. Results: The mean serum OPG level in patients with bladder cancer was approximately 3-fold higher than that in normal donors. The serum OPG level in patients with muscle-invasive bladder cancer was higher than that in superficial bladder cancer. Furthermore, serum level of OPG in patients with metastatic bladder cancer was higher than that in muscle-invasive bladder cancer. Serum OPG level in Grade 2 bladder cancer was higher than that in Grade 1 cancer. Moreover, serum OPG level in Grade 3 bladder cancer was higher than that in Grade 2 cancer. Patients with superficial bladder cancer with low serum OPG level had a longer postoperative tumor-free rate than those with high level in the 5-year follow-up. In addition, patients with muscle-invasive bladder cancer with low serum OPG level had a higher disease-specific survival rate when compared with patients with high level in the 5-year follow-up. There was an inverse correlation between serum OPG level and anti-autologous tumor cytotoxic activity. Conclusions: The present study is the first to demonstrate that the serum OPG level correlates with the stage/grade of bladder cancer, and that elevated level serum OPG predicted early recurrence in patient with bladder cancer. These findings suggest that serum OPG level may be used as a prognostic parameter in patients with bladder cancer, and that OPG may be a molecular therapeutic target in bladder cancer. No significant financial relationships to disclose.