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

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 center dot 50ng/ml, range: 0146 center dot 78ng/ml), relative to age-matched controls (n=27; mean: 2 center dot 66ng/ml, range: 05 center dot 96ng/ml), although this did not reach statistical significance. Notably, patients with abnormally high levels of N-cadherin (>6ng/ml) had decreased progression-free survival (P=0 center dot 036; hazard ratio: 1 center dot 94) and overall survival (P=0 center dot 002; hazard ratio: 3 center dot 15), when compared with patients with normal N-cadherin levels (6ng/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.