Evaluation of epithelial-mesenchymal transitioned circulating tumor cells in patients with resectable gastric cancer: Relevance to therapy response

摘要

AIM: To evaluate the epithelial-to-mesenchymal transition (EMT) of circulating tumor cells (CTCs) in gastric cancer patients. METHODS: We detected tumor cells for expression of four epithelial (E+) transcripts (keratins 8, 18, and 19 and epithelial cell adhesion molecule) and two mesenchymal (M+) transcripts (Vimentin and Twist) by a quantifiable, dual-colorimetric RNA-in situ hybridization assay. Between July 2014 and October 2014, 44 patients with gastric cancer were recruited for CTC evaluation. Blood samples were obtained from selected patients during the treatment course [before surgery, after surgery and at the 6th cycle of XELOX based chemotherapy (about 6 mo postoperatively)]. RESULTS: We found the EMT phenomenon in which there were a few biphenotypic E+/M+ cells in primary human gastric cancer specimens. Of the 44 patients, the presence of CTCs was reported in 35 (79.5%) patients at baseline. Five types of cells including from exclusively E+ CTCs to intermediate CTCs and exclusively M+ CTCs were identified (4 patients with M+ CTCs and 10 patients with M+ or M+ > E+ CTCs). Further, a chemotherapy patient having progressive disease showed a proportional increase of mesenchymal CTCs in the post-treatment blood specimens. We used NCI-N87 cells to analyze the linearity and sensitivity of CanPatrolTM system and the correlation coefficient (R2) was 0.999. CONCLUSION: The findings suggest that the EMT phenomenon was both in a few cells of primary tumors and abundantly in CTCs from the blood of gastric cancer patients, which might be used to monitor therapy response.