Glycosylation of ascites-derived exosomal CD133: a potential prognostic biomarker in patients with advanced pancreatic cancer

Cancer cells surviving in ascites exhibit cancer stem cell (CSC)-like features. This study analyzed the expression of the CSC marker CD133 in the ascites-derived exosomes obtained from patients with unresectable pancreatic cancer. In addition, inverse correlation of CD133 expression with prognosis was examined. Of the 133 consecutive patients, 19 patients were enrolled in the study. Exosomes derived from the malignant ascites demonstrated higher density and wider variation in size than those from non-malignant ascites. Western blot revealed enhanced expression of CD133 in exosomes obtained from patients with pancreatic cancer compared to those obtained from patients with gastric cancer or liver cirrhosis. A xenograft mouse model with malignant ascites was established by intraperitoneal inoculation of human pancreatic cancer cells in nude mice. Results obtained from the human study were reproduced in the mouse model. Statistically significant equilateral correlation was identified between the band intensity of CD133 in western blot and overall survival of patients. Lectin microarray analyses revealed glycosylation of CD133 by sialic acids as the major glycosylation among diverse others responsible for the glycosylation of exosomal CD133. These findings suggest that highly glycosylated CD133 in ascites-derived exosomes as a potential biomarker for better prognosis of patients with advanced pancreatic cancer.