Strong immunoexpression of dickkopf-1 is associated with response to bortezomib in multiple myeloma

Abstract

The predictive significance of osteolysis-related proteins was evaluated in bortezomib-treated multiple myeloma. The clinicopathological characteristics were collected retrospectively. Immunohistochemistry was performed for analyzing receptor activator of NF-kappaB ligand (RANKL), osteoprotegerin (OPG), macrophage inflammatory protein 1 alpha (MIP1alpha), and dickkopf-1 (DKK1) expression. Among clinicopatholgical characteristics, osteolytic lesion was associated with higher response to bortezomib treatment (79% vs. 46%). High DKK1 expression was significantly correlated with osteolytic lesion (p = .003), whereas RANKL, OPG, and MIP1alpha were not. In high DKK1 expression, higher response to bortezomib was observed (84% vs. 44%). In multivariate analysis, high DKK1 expression was associated with better response to bortezomib (p = .005). Patients with high DKK1 expression had longer median progression-free survival (PFS) and overall survival (OS) after bortezomib treatment. In multivariate analysis, high DKK1 expression was an independent prognostic factor of favorable PFS (p = .027) and OS (p = .035). In multiple myeloma treated with bortezomib, expression status of DKK1 may be a useful predictive marker.