Abstract
Background: Recent studies showed a relevant role of hematogenous spread in ovarian cancer and the interest of circulating tumor cells (CTCs) monitoring as a prognosis marker. The aim of the present study was the characterization of CTCs from ovarian cancer patients, paying special attention to cell plasticity characteristics to better understand the biology of these cells. Methods: CTCs isolation was carried out in 38 patients with advanced high-grade serous ovarian cancer using in parallel CellSearch and an alternative EpCAM-based immunoisolation followed by RT-qPCR analysis to characterize these cells. Results: Epithelial CTCs were found in 21% of patients, being their presence higher in patients with extraperitoneal metastasis. Importantly, this population was characterized by the expression of epithelial markers as MUC1 and CK19, but also by genes associated with mesenchymal and more malignant features as TIMP1, CXCR4 and the stem markers CD24 and CD44. In addition, we evidenced the relevance of TIMP1 expression to promote tumor proliferation, suggesting its interest as a therapeutic target. Conclusions: Overall, we evidenced the utility of the molecular characterization of EpCAM+ CTCs from advanced ovarian cancer patients to identify biomarkers with potential applicability for disseminated disease detection and as therapeutic targets such as TIMP1.
Highlights
Ovarian cancer is an important public health issue in Western countries [1]
circulating tumor cells (CTCs) Enumeration by Cellsearch System was Higher in Patients with a More Aggressive Disease
As we previously reported in other tumor subtypes, firstly we confirmed the presence the CTCs population in our cohort of patients by RT‐qPCR after the immunoisolation of EpCAM
Summary
The majority of malignant ovarian tumors (90%) are carcinomas, being high-grade serous ovarian carcinoma (HGSOC) the most common subtype [1]. This tumor has a fatal prognosis with an overall 5-year survival rate lower than 40% because most of the patients present advanced stage disease and tumor masses in the abdomen beyond the pelvis at diagnosis [2]. Conclusions: Overall, we evidenced the utility of the molecular characterization of EpCAM+ CTCs from advanced ovarian cancer patients to identify biomarkers with potential applicability for disseminated disease detection and as therapeutic targets such as TIMP1
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