title: Circulating N-cadherin levels are a negative prognostic indicator in patients with multiple myeloma.
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.
authors: Myeloma Research Laboratory, Department of Haematology, Centre for Cancer Biology, SA Pathology, Adelaide, SA, Australia.
authors: Kate
authors: K
authors: Vandyke
authors: Annie W S
authors: AW
authors: Chow
authors: Sharon A
authors: SA
authors: Williams
authors: Luen B
authors: LB
authors: To
authors: Andrew C W
authors: AC
authors: Zannettino
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood; D015820:Cadherins / Q000097:blood* / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000097:blood* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D009367:Neoplasm Staging; D010950:Plasma Cells / Q000378:metabolism / Q000473:pathology; D011379:Prognosis
chemical_list: D014408:Biomarkers, Tumor; D015820:Cadherins