Assessment of a fragment of e-cadherin as a serum biomarker with predictive value for prostate cancer

Abstract

In prostate cancer, biomarkers may provide additional value above standard clinical and pathology parameters to predict outcome after specific therapy. The purpose of this study is to evaluate an 80 kDa fragment of the cell adhesion molecule e-cadherin as a serum biomarker. A broad spectrum of prostate cancer serum samples, representing different stages of prostate cancer disease, including benign prostatic hyperplasia (BPH), localised (Loc PCA) and metastatic prostate cancer (Met PCA), was examined for the cleaved product. There is a significant difference in the expression level of the 80 kDa fragment in the serum of healthy individuals vs patients with BPH and between BPH vs Loc PCA and Met PCA (Po0.001). Highest expression levels are observed in advanced metastatic disease. In the cohort of Loc PCA cases, there was no association between the 80 kDa serum concentration and clinical parameters. Interestingly, patients with an 80 kDa level of 47.9 mg l À1 at the time of diagnosis have a 55-fold higher risk of biochemical failure after surgery compared to those with lower levels. This is the first report of the application of an 80 kDa fragment of e-cadherin as a serum biomarker in a broad spectrum of prostate cancer cases. At an optimised cutoff, high expression at the time of diagnosis is associated with a significantly increased risk of biochemical failure, potentially supporting its use for a tailored follow-up protocol for those patients.

Soluble E-cadherin and IL-6 serum levels in patients affected by prostate cancer before and after prostatectomy

“…sE-cad levels found in preoperative serum samples are in the range reported in the literature in patients affected by this or other types of cancers (5,13,15,16,28). Values determined in patients were significantly higher than those observed in healthy subjects according to reports by other authors (5,15,16,18,28).…”

“…It has been reported that sE-cad is involved in stimulation of invasion in a paracrine manner, in promotion of cell junction disruption and of cell dissemination thereby inducing the migratory phenotype (19). Moreover, the highest expression levels of sE-cad have been found in patients with metastatic cancers, and high levels at the time of diagnosis are associated with a significant risk of biochemical failure (16)(17)(18) (17). Regarding interleukins (IL), they are pleiotropic cytokines with a wide range of biological activities including immune regulation, hematopoiesis, inflammation and oncogenesis (20).…”

“…E-cad ectodomain shedding determines the release into the body fluids of a soluble 80 kDa E-cad fragment (sE-cad) (12). High sE-cad serum levels are present in cancer patients when compared with those of healthy individuals and they are significantly associated with metastasis, recurrence, and prognosis in some malignancies, including PCa (13)(14)(15)(16)(17)(18). It has been reported that sE-cad is involved in stimulation of invasion in a paracrine manner, in promotion of cell junction disruption and of cell dissemination thereby inducing the migratory phenotype (19).…”

Beyond prostate-specific antigen: alternate serum markers

“…122 E-cadherin, b-catenin and matrix metalloproteinases are also involved in altered cell adhesion and cellular migration and appear to be promising biological markers associated with disease aggressiveness. 123,124 Other potential protein biomarkers include inhibitors of metalloproteinases, 125 hepatocyte growth factor, 126 macrophage migration inhibitory factor, 127 progastrin-releasing peptide 128 and 50.8 kDa protein. 129 Additional growth factors, including insulin-like growth factor (IGF)-I, IGF-II and IGF-binding protein-3 (BP-3) have been implicated in the etiology of both benign and malignant disease.…”

β‐catenin mediates alteration in cell proliferation, motility and invasion of prostate cancer cells by differential expression of E‐cadherin and protein kinase D1

“…Decreased E-cadherin expression is considered to be a central event in the disruption of the normal cell-cell adhesion required for the acquisition of the invasive and metastatic phenotype of various epithelial neoplasms, including PC [Bussemakers et al, 1992;Paul et al, 1997]. Aberrant E-cadherin expression was associated with a larger tumor size [Rubin et al, 2001], a higher tumor grade and stage, and an increased risk of disease recurrence after prostatectomy [Kuefer et al, 2005].…”