Circulating N-cadherin levels are a negative prognostic indicator in patients with multiple myeloma
Date
2013
Authors
Vandyke, K.
Chow, A.
Williams, S.
To, L.
Zannettino, A.
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Journal article
Citation
British Journal of Haematology, 2013; 161(4):499-507
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Kate Vandyke, Annie W.S. Chow, Sharon A. Williams, Luen B. To and Andrew C.W. Zannettino
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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.
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© 2013 John Wiley & Sons Ltd