The impact of EpCAM expression on response to chemotherapy and clinical outcomes in patients with epithelial ovarian cancer

Abstract

Epithelial ovarian cancer is a highly lethal malignancy; moreover, overcoming chemoresistance is the major challenging in treating ovarian cancer patients. The cancer stem cell (CSC) hypothesis considers CSCs to be the main culprits in driving tumor initiation, metastasis, and resistance to conventional therapy. Although growing evidence suggest that CSCs are responsible for chemoresistance, the contribution of CSC marker EpCAM to resistance to chemotherapy remains unresolved.Here we have demonstrated that ovarian cancers containing high levels of EpCAM have a significantly much lower probability of achieving overall responsive rates after first-line chemotherapy. In addition, multivariate analysis revealed that EpCAM expression is an independent risk factor for chemoresistance, indicating that EpCAM expression is a predictive biomarker of chemotherapeutic response. Consistent with these clinical observations, in vitro assays, we found that the subpopulation of EpCAM-positive ovarian cancer cells shows a significantly higher viability compared with EpCAM-negative cells in response to cisplatin treatment by preventing chemotherapy-induced apoptosis, which is regulated by EpCAM-Bcl-2 axis. Furthermore, in an in vivo mouse model, platinum agents preferentially eliminated EpCAM-negative cells in comparison with EpCAM-positive cells, suggesting that the remaining subpopulation of EpCAM-positive cells contributes to tumor recurrence after chemotherapy. Finally, we also found that an increased expression of EpCAM is associated with poor prognosis in ovarian cancer patients.Our findings highlight the clinical significance of EpCAM in the resistance to chemotherapy and provide a rationale for EpCAM-targeted therapy to improve chemoresistance. Targeting EpCAM should be a promising approach to effectively extirpate the CSCs as the putative root of ovarian cancer.

Downregulation of MYPT1 increases tumor resistance in ovarian cancer by targeting the Hippo pathway and increasing the stemness

“…4e and Additional file 3: Figure S5d). Moreover, we measured the expression levels of the CSC markers CD44 and EPCAM [38][39][40], showing also an upregulation only in MYPT1-depleted ES-2 and SKOV3 cells (Fig. 4e).…”

IL‑6 prevents CXCL8‑induced stimulation of EpCAM expression in ovarian cancer cells

“…Increased expression of EpCAM also contributes to increased viability of cancer cells in vitro and resistance to platinium-based chemotherapy in patients with ovarian cancer. Finally, increased expression of EpCAM is associated with a poor prognosis in patients with ovarian cancer (24). Therefore, EpCAM has begun to be a promising therapeutic target in a number of antibody-based clinical trials.…”

Novel Therapeutic Strategies for Ovarian Cancer Stem Cells

“…EpCAM has been recognized as an additional marker for CSCs in different tumor types (55). High expression of EpCAM in OC is associated with tumor recurrence, chemoresistance and poor patient prognosis (117). Cells co-expressing CD24, CD44, and EpCAM showed stem cell-like characteristics, high tumorigenicity in vivo as well as enhanced migration, invasion and colony-formation in vitro and this population could be enriched by chemotherapy (50,118).…”