Pancreatic Juice Exosomal MicroRNAs as Biomarkers for Detection of Pancreatic Ductal Adenocarcinoma
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Pancreatic ductal adenocarcinoma (PDAC) is a lethal neoplasm because of difficulties in early detection. Several studies have recently suggested that exosomes may have potential as novel biomarkers. This study aimed to isolate exosomes from pancreatic juice and to investigate whether exosomal microRNAs (ex-miRs) could be used as biomarkers for PDAC.
Pancreatic juice was collected from patients with PDAC and chronic pancreatitis (CP) by endoscopic retrograde pancreatography. Exosomes were extracted by ultracentrifugation. The presence of exosomes was confirmed by electron microscopy and Western blotting using anti-CD63, -CD81, and -TSG101 antibodies. Relative levels of ex-miR-21 and ex-miR-155 were quantified and compared between PDAC and CP patients.
A total of 35 pancreatic juice samples (27 PDAC and 8 CP) were collected. Relative levels of both ex-miR-21 and ex-miR-155 were significantly higher in PDAC patients compared with CP patients (p < 0.001 and p = 0.008, respectively). By contrast, no significant difference was apparent in relative levels of miR-21 and miR-155 in whole pancreatic juice from PDAC patients compared with CP patients (p = 0.08 and p = 0.61, respectively). Ex-miR-21 and ex-miR-155 levels discriminated PDAC patients from CP patients with area under the curve values of 0.90 and 0.89, respectively. The accuracies of ex-miR-21 levels, ex-miR-155 levels, and pancreatic juice cytology were 83%, 89%, and 74%, respectively. When combining the results of ex-miR profiling with pancreatic juice cytology, the accuracy was improved to 91%.
We successfully extracted exosomes from pancreatic juice. Ex-miRs, including ex-miR-21 and ex-miR-155, in pancreatic juice may be developed as biomarkers for PDAC.
SN, TO, YN, and YG contributed to establishing the study population database and performed data extraction and analysis. YS, TO, YM, KN, YM, HO, MG, and MN contributed to study conception and design and performed the pancreatectomy and follow-up of the study population. KS and YO made the pathological diagnoses. SN wrote the manuscript. YS and TO contributed to the interpretation of results and manuscript revision. All authors discussed the results and commented on the manuscript. YS, TO, YM, KN, YM, HO, MG, and MN provided the final approval for this article.
This study was supported by a Grant-in-Aid for Scientific Research (Grant numbers 15K10186, 17K10637, 17K10636) and a JFE (The Japanese Foundation for Research and Promotion of Endoscopy) grant.
So Nakamura, Yoshihiko Sadakari, Takao Ohtsuka, Takafumi Okayama, Yohei Nakashima, Yoshitaka Gotoh, Kiyoshi Saeki, Yasuhisa Mori, Kohei Nakata, Yoshihiro Miyasaka, Hideya Onishi, Yoshinao Oda, Michael Goggins, and Masafumi Nakamura disclosed no financial relationships relevant to this publication.
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