Soluble E‐cadherin as a serum biomarker candidate: Elevated levels in patients with late‐stage colorectal carcinoma and FAP

Abstract

Various strategies have been tested to identify serum biomarkers in patients with cancer. Recently, the entire of proteins released by cultured tumor cells into the media, the so-called secretome, has been suggested as a promising source for biomarker discovery. Ectodomains of membrane proteins cleaved from the cell surface represent a surprisingly abundant and apparently stable subset of this subproteome. Aiming for the detection of serum biomarkers for patients with colorectal cancer (CRC), we have previously detected significant amounts of the soluble form of E-cadherin in the secretomes of CRC cells. Here, we report a comprehensive analysis of sE-cadherin levels in sera from patients with CRC, colorectal adenoma, inflammatory bowel disease and familial adenomatous polyposis (FAP). Whereas mean sE-cadherin levels in patients with inflammatory bowel disease (mean: 4.7 μg/ml, SD: 1.5 μg/ml), with adenomas (mean: 4.6 μg/ml, SD: 3.0 μg/ml) and early stage cancers (mean: 4.9 μg/ml, SD: 4.7 μg/ml) do not significantly differ from healthy controls (mean: 4.8 μg/ml, SD: 1.9 μg/ml), patients with Stage III and Stage IV carcinomas display a significant increase (mean: 6.1 μg/ml, SD: 2.6 μg/ml). In individual patients with late-stage CRC, sE-cadherin serum levels directly reflect their disease status over time. These findings suggest a potential application of sE-cadherin as an alternative diagnostic biomarker for monitoring disease particularly in patients with carcinoembryonic antigen negative tumors. In patients with FAP, on the other hand, we also detected a significant increase of serum sE-cadherin levels (mean: 5.8 μg/ml, SD: 2.8 μg/ml), but this was regardless of their tumor load and colectomy status.