| 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. |
