Abstract 2660: Glycosylation of ascites-derived exosomal CD133 is a potential prognostic biomarker in patients with advanced pancreatic cancer

Abstract

Abstract Background: It is known that cancer cells surviving in ascites show cancer stem cell (CSC)-like features. The CSC-like cells abundantly secrete extracellular vesicles called exosomes, which may play important roles in maintaining tumor-specific microenvironment in the abdominal cavity. We have demonstrated that exosomes were rich in malignant ascites of patients with advanced pancreatic cancer, and that the exosomes contained much CD133 among the CSC-associated proteins examined. Of note, the expression level of exosomal CD133 was highest in pancreatic cancer patients compared with that in gastric cancer patients and those with liver cirrhosis. Thus, the aim of this study was to assess whether expression levels of CD133 in the ascites-derived exosomes obtained from pancreatic cancer patients inversely correlate with their prognosis. Methods: 133 patients with pancreatic cancer who visited the Center for Multidisciplinary Treatment of Cancer in Kurume University Hospital from June, 2014 to June, 2017 were enrolled into this study. Informed consent was obtained from all patients in accordance with the principles stated in the Declaration of Helsinki and the guidelines of the Ethical Committee of Kurume University. Exosomes derived from consecutive 19 patients with malignant ascites of 133 patients were purified by using ExoQuick kit (System Biosciences). Western blotting and densitometry were performed to detect CD133 and to determine its expression levels, respectively. We focused on possible relationship between band intensity of highly glycosylated CD133 (defined as “upper band”) and overall survival of the patients. Results: Median overall survival of 19 patients with malignant ascites was 256 days (45-1031 days), while that of 133 patients was 225 days (4-1617 days). Then, the 19 patients showing worse prognosis were subjected to densitometric analysis of intensity of the upper band for CD133, reflecting glycosylation of the molecule. As a result, there was an equilateral correlation between the upper band density of CD133 and overall survival (p=0.0309). The finding suggested that longer survival was predicted even for the advanced pancreatic cancer patients with malignant ascites when increased density in the upper band of ascites-derived exosomal CD133 was seen. Conclusions: Although the number of patients was limited and glycosylation profile of the upper band was under investigation in this study, it is suggested that glycosylation of CD133 derived from exosomes in malignant ascites may be useful in selecting patients with better prognosis who are feasible to receive further chemotherapeutic treatment for advanced pancreatic cancer. Citation Format: Takahiko Sakaue, Hironori Koga, Hideki Iwamoto, Yasuko Imamura, Toru Nakamura, Mitsuhiko Abe, Fumitaka Wada, Atsutaka Masuda, Toshimitsu Tanaka, Masaru Fukahori, Tomoyuki Ushijima, Yoshinobu Okabe, Tatsuyuki Kakuma, Takuji Torimura. Glycosylation of ascites-derived exosomal CD133 is a potential prognostic biomarker in patients with advanced pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2660.