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

Leuk Lymphoma. 2018 Nov;59(11):2670-2678. doi: 10.1080/10428194.2018.1443331. Epub 2018 Mar 27.

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-κB ligand (RANKL), osteoprotegerin (OPG), macrophage inflammatory protein 1 alpha (MIP1α), 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 MIP1α 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.

Keywords: Multiple myeloma; bortezomib; dickkopf-1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / therapeutic use*
  • Biomarkers, Tumor / metabolism*
  • Bortezomib / therapeutic use*
  • Female
  • Follow-Up Studies
  • Humans
  • Intercellular Signaling Peptides and Proteins / metabolism*
  • Male
  • Middle Aged
  • Multiple Myeloma / drug therapy
  • Multiple Myeloma / metabolism
  • Multiple Myeloma / pathology*
  • Prognosis
  • Retrospective Studies
  • Survival Rate

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • DKK1 protein, human
  • Intercellular Signaling Peptides and Proteins
  • Bortezomib