Circulating N-cadherin levels are a negative prognostic indicator in patients with multiple myeloma

Br J Haematol. 2013 May;161(4):499-507. doi: 10.1111/bjh.12280. Epub 2013 Feb 26.

Abstract

N-cadherin (cadherin 2, type 1, N-cadherin (neuronal); CDN2) is a homotypic adhesion molecule that is upregulated in breast, prostate and bladder cancer. Here we investigated the prognostic significance of upregulated N-cadherin expression in multiple myeloma (MM). Our results indicate that N-cadherin protein and gene expression is abnormally increased in trephine biopsies and CD38(++) /CD138(+) plasma cells from MM patients, when compared with those of normal donors. In addition, levels of circulating N-cadherin were elevated in a subset of patients with MM (n = 81; mean: 14·50 ng/ml, range: 0-146·78 ng/ml), relative to age-matched controls (n = 27; mean: 2·66 ng/ml, range: 0-5·96 ng/ml), although this did not reach statistical significance. Notably, patients with abnormally high levels of N-cadherin (>6 ng/ml) had decreased progression-free survival (P = 0·036; hazard ratio: 1·94) and overall survival (P = 0·002; hazard ratio: 3·15), when compared with patients with normal N-cadherin levels (≤6 ng/ml). Furthermore, multivariate analyses revealed that the combination of N-cadherin levels and International Staging System (ISS) was a more powerful prognostic indicator than using ISS alone. Collectively, our studies demonstrate that circulating N-cadherin levels are a viable prognostic marker for high-risk MM patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / blood
  • Cadherins / blood*
  • Cadherins / genetics
  • Female
  • Humans
  • Male
  • Middle Aged
  • Multiple Myeloma / blood*
  • Multiple Myeloma / genetics
  • Multiple Myeloma / mortality
  • Multiple Myeloma / pathology
  • Neoplasm Staging
  • Plasma Cells / metabolism
  • Plasma Cells / pathology
  • Prognosis

Substances

  • Biomarkers, Tumor
  • Cadherins