Abstract 3137: Pancreatic juice biomarker for detection of early stage pancreatic cancer using tumor-specific exosomal microRNAs

Abstract

Abstract Background: Pancreatic ductal adenocarcinoma (PDAC) is a lethal neoplasm because of difficulties in early detection. Therefore, identification of biomarkers for early diagnosis of PDAC is crucial. Several studies have reported that exosomes in blood derived from patients with PDAC might contain the tumor-specific microRNAs, but such microRNAs have not been established as biomarkers in the clinical setting. The aims of this study were to identify tumor-specific exosomal microRNAs from pancreatic juice, which was in contact with PDAC in the pancreatic duct, and to investigate whether exosomal microRNAs could be used as biomarkers for detection of early PDAC. Methods: Pancreatic juice was collected from the patients who underwent Endoscopic Retrograde Cholangiopancreatography in Kurume University Hospital. Informed consent was obtained from all the patients in accordance with the principles stated in the Declaration of Helsinki and the guidelines of the Ethical Committee of Kurume University. Exosomes in pancreatic juice derived from pancreatic cancer and non-pancreatic cancer patients were extracted by ultracentrifugation. To confirm the presence of exosomes, expression of known internal control proteins in exosomes was assessed by Western blotting. By transmission electron microscopy (TEM), morphologic difference between the pancreatic cancer and the non-pancreatic cancer exosomes was evaluated. Characteristics of exosomes, such as the number of exosomes, size and the unevenness, in pancreatic cancer and non-pancreatic cancer were examined by Nanoparticle Tracking Analysis (NTA). Furthermore, we performed microRNA array analysis by using PDAC cell line-derived exosomal microRNAs and narrowed down the pancreatic cancer cell-specific microRNAs in vivo. Results: Successful purification of exosomes in pancreatic juice derived from pancreatic cancer and non-pancreatic cancer patients was confirmed by monitoring exosome-specific proteins such as CD63, CD9, CD81, and HSP70. Moreover, the presence of exosomes was confirmed by TEM and NTA. Three promising pancreatic cancer cell-specific microRNAs were identified by our original microarray analysis. Conclusions: We first demonstrated the existence of PDAC-specific exosomal microRNAs from pancreatic juice. The finding suggests that exosomal microRNAs may be a potential biomarker for detection of early stage pancreatic cancer. Citation Format: Takahiko Sakaue, Hideki Iwamoto, Hironori Koga, Yasuko Imamura, Toru Nakamura, Atsutaka Masuda, Toshimitsu Tanaka, Hiroyuki Suzuki, Tomoyuki Ushijima, Yoshinobu Okabe, Takuji Torimura. Pancreatic juice biomarker for detection of early stage pancreatic cancer using tumor-specific exosomal microRNAs [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3137.