Circulating tumor cells expressing cancer stem cell marker CD44 as a diagnostic biomarker in patients with gastric cancer

Abstract

Epithelial cell adhesion molecule (EpCAM) is a marker for circulating tumor cells (CTCs) in various types of cancer, while cluster of differentiation 44 (CD44) is a marker for gastric cancer (GC) stem cells. To evaluate the clinical significance of CD44 ⁺ CTCs in patients with GC in the present study, the number of EpCAM ⁺CD44 ⁺ and EpCAM ⁺CD44 ⁻ cells were detected in the peripheral blood of 26 GC patients and 12 healthy volunteers using flow cytometry. The number (mean ± standard deviation) of EpCAM ⁺CD44 ⁺ cells in the GC patients and healthy volunteers was 69.9±52.0 and 0.91±2.10, respectively (P=0.0001), while that of EpCAM ⁺CD44 ⁻ cells was 59.1±88.0 and 9.83±9.91, respectively (P=0.0313). The sensitivity and specificity of EpCAM ⁺CD44 ⁺ cell detection for the identification of GC patients were 92.3 and 100%, respectively. By contrast, the values of EpCAM ⁺CD44 ⁻ cell detection were 76.9 and 83.3%, respectively. The number of EpCAM ⁺CD44 ⁺ cells in the GC patients was correlated with the disease stage (P=0.0423), the depth of the tumor (P=0.0314) and venous invasion (P=0.0184) in the resected tumor specimens, while the number of EpCAM ⁺CD44 ⁻ cells did not correlate with any clinicopathological factors. The number of EpCAM ⁺CD44 ⁺ cells significantly decreased following surgical resection of the tumor or induction of systemic chemotherapy. Additionally, atypical cells with a high nuclear to cytoplasmic ratio were morphologically detected in the sorted EpCAM ⁺CD44 ⁺ cells. These results suggested that CD44 ⁺ CTCs, but not CD44 ⁻ CTCs, reflect the malignant status of the primary tumor in patients with GC, providing a candidate biomarker for diagnosis and treatment response.