Elevated soluble E-cadherin during the epithelial-mesenchymal transition process and as a diagnostic marker in colorectal cancer

Colorectal Cancer
17/06/2020

Zhu S, et al. Gene 2020.

ABSTRACT

Epithelial-mesenchymal transition (EMT) plays a crucial role in colorectal cancer (CRC) metastasis. Soluble E-cadherin (sE-cadherin) is a peptide degradation product of the E-cadherin, a key epithelial molecule of EMT. However, it is not known if elevated levels of sE-cadherin also occur during EMT. And the study of sE-cadherin in colorectal cancer is rare. The purpose of the study was to evaluate the relationship between sE-cadherin and EMT in CRC and to evaluate the diagnostic value of


sE-cadherin as a serum marker for CRC. Transforming growth factor-β1 (TGF-β1) was used to induce EMT in HT29 and SW480 cells. The cells treated with TGF-β1 showed morphological and biological behavior changes consistent with EMT. Western blot and ELISA showed the levels of sE-cadherin were increased during EMT in CRC cells. In addition, we intravenously injected luciferase-labeled SW480 cells into nude mice to construct CRC metastasis model. Following the elongation of time, the fluorescence intensity of the experimental group was gradually increased. Correspondingly, the serum concentration of sE-cadherin also increased during CRC metastasis in mice. Furthermore, compared to healthy subjects, significantly higher levels of serum sE-cadherin were also observed in CRC patients and correlated with clinicopathological features. For discriminating CRC from healthy controls, the area under the receiver operating characteristic (ROC) curve (AUC) of sE-cadherin was 0.853, while the optimal cut-off point was set at 5928.16ng/ml, the diagnostic sensitivity was 73.9% and the specificity was 80%. Compared with current commercial biomarkers (CEA, CA19-9 and CA125), the diagnostic performance of sE-cadherin was highest. Combined sE-cadherin and CEA raised the sensitivity to 82.4%. Serum sE-cadherin level can be used as a potential diagnostic biomarker of CRC.