Pancreatic Juice Exosomal MicroRNAs as Biomarkers for Detection of Pancreatic Ductal Adenocarcinoma

So Nakamura, Yoshihiko Sadakari, Ohtsuka Takao, Takafumi Okayama, Yohei Nakashima, Yoshitaka Gotoh, Kiyoshi Saeki, Yasuhisa Mori, Kohei Nakata, Yoshihiro Miyasaka, Hideya Ohnishi, Yoshinao Oda, Michael Goggins, Masafumi Nakamura

Research output: Contribution to journalArticle

Abstract

Background: 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. Methods: 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. Results: 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%. Conclusions: 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.

Original languageEnglish
Pages (from-to)2104-2111
Number of pages8
JournalAnnals of Surgical Oncology
Volume26
Issue number7
DOIs
Publication statusPublished - Jul 15 2019

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Pancreatic Juice
MicroRNAs
Adenocarcinoma
Biomarkers
Exosomes
Chronic Pancreatitis
Cell Biology
Ultracentrifugation
Area Under Curve
Electron Microscopy
Western Blotting

All Science Journal Classification (ASJC) codes

  • Surgery
  • Oncology

Cite this

Pancreatic Juice Exosomal MicroRNAs as Biomarkers for Detection of Pancreatic Ductal Adenocarcinoma. / Nakamura, So; Sadakari, Yoshihiko; Takao, Ohtsuka; Okayama, Takafumi; Nakashima, Yohei; Gotoh, Yoshitaka; Saeki, Kiyoshi; Mori, Yasuhisa; Nakata, Kohei; Miyasaka, Yoshihiro; Ohnishi, Hideya; Oda, Yoshinao; Goggins, Michael; Nakamura, Masafumi.

In: Annals of Surgical Oncology, Vol. 26, No. 7, 15.07.2019, p. 2104-2111.

Research output: Contribution to journalArticle

Nakamura, So ; Sadakari, Yoshihiko ; Takao, Ohtsuka ; Okayama, Takafumi ; Nakashima, Yohei ; Gotoh, Yoshitaka ; Saeki, Kiyoshi ; Mori, Yasuhisa ; Nakata, Kohei ; Miyasaka, Yoshihiro ; Ohnishi, Hideya ; Oda, Yoshinao ; Goggins, Michael ; Nakamura, Masafumi. / Pancreatic Juice Exosomal MicroRNAs as Biomarkers for Detection of Pancreatic Ductal Adenocarcinoma. In: Annals of Surgical Oncology. 2019 ; Vol. 26, No. 7. pp. 2104-2111.
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abstract = "Background: 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. Methods: 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. Results: 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{\%}. Conclusions: 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.",
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T1 - Pancreatic Juice Exosomal MicroRNAs as Biomarkers for Detection of Pancreatic Ductal Adenocarcinoma

AU - Nakamura, So

AU - Sadakari, Yoshihiko

AU - Takao, Ohtsuka

AU - Okayama, Takafumi

AU - Nakashima, Yohei

AU - Gotoh, Yoshitaka

AU - Saeki, Kiyoshi

AU - Mori, Yasuhisa

AU - Nakata, Kohei

AU - Miyasaka, Yoshihiro

AU - Ohnishi, Hideya

AU - Oda, Yoshinao

AU - Goggins, Michael

AU - Nakamura, Masafumi

PY - 2019/7/15

Y1 - 2019/7/15

N2 - Background: 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. Methods: 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. Results: 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%. Conclusions: 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.

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