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

摘要

Epithelial cell adhesion molecule (EpCAM) is a marker for circulating tumor cells (CTCs) in various types of cancer, while cluster of differentiation /I/1 (CD44) is a marker for gastric cancer (GC) stem cells. To evaluate the clinical significance of CD'1'l CTCs in patients with GC in the present study, the number of EpCAWCD4(+) and EpCAM CD44cells 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 EpCANPCD44(-) 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.