title: 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.
authors.affiliation: Department of Surgery and Science, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, Toyama 930-0194, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Watanabe
authors.affiliation: Department of Surgery and Science, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, Toyama 930-0194, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Okumura
authors.affiliation: Department of Surgery and Science, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, Toyama 930-0194, Japan.
authors.forename: Katsuhisa
authors.initials: K
authors.lastname: Hirano
authors.affiliation: Department of Surgery and Science, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, Toyama 930-0194, Japan.
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Yamaguchi
authors.affiliation: Department of Surgery and Science, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, Toyama 930-0194, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Sekine
authors.affiliation: Department of Surgery and Science, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, Toyama 930-0194, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Nagata
authors.affiliation: Department of Surgery and Science, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, Toyama 930-0194, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Tsukada
keywords: circulating tumor cells; cluster of differentiation 44; epithelial cell adhesion molecule; flow cytometry; gastric cancer