CD44+ Circulating Tumor Endothelial Cells Indicate Poor Prognosis in Pancreatic Ductal Adenocarcinoma After Radical Surgery: A Pilot Study

BACKGROUND: Circulating tumor endothelial cells (CTECs) are cells that originate from tumor endothelial cells (TECs) of blood vessels and are shed into peripheral blood. Some studies have shown that CTECs are associated with tumor angiogenesis, growth and indicate prognosis in patients with malignant solid tumor. However, the role of CTECs especially the phenotype of CTECs in pancreatic adenocarcinoma (PDAC) is still not clear. We investigated the relationship between CTECs and patients’ prognosis. METHODS: A total of 73 patients with resectable PDAC were enrolled in our research and underwent radical surgery. Peripheral venous blood samples were collected before surgery, on postoperative day (POD) 7 and on postoperative month (POM) 1, respectively. We used integrated subtraction enrichment and immunostaining-fluorescence in situ hybridization (SE-iFISH) platform to identify and enumerate CTECs. Immunofluorescence was used to identify CTECs expressing CD44 and vimentin. RESULTS: In patients with early tumor recurrence (DFS< 6 months), the preoperative CD44+ CTEC levels showed significantly higher (P = 0.023). Univariate and multivariate analysis showed that history of diabetes [HR 2.656 (1.194–5.908), P = 0.017], numbers of positive lymph nodes [HR 1.871 (1.388–2.522), P < 0.001], preoperative numbers of CD44+ CTECs [HR 1.216 (1.064–1.390), P = 0.004], and POM1 CA19-9 level [HR 1.002 (1.001–1.002), P < 0.001] were independent prognostic factors for DFS. CONCLUSION: The detection of CD44+CTECs in patients with resectable PDAC preoperatively could be an independent predictor of shorter DFS after radical surgery.