An elevated expression of serum exosomal microRNA-191, − 21, −451a of pancreatic neoplasm is considered to be efficient diagnostic marker

Abstract Background Pancreatic cancer is associated with an extremely poor prognosis, so new biomarkers that can detect the initial stages are urgently needed. The significance of serum microRNA (miR) levels in pancreatic neoplasm such as pancreatic cancer and intraductal papillary mucinous neoplasm...

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Main Authors: Takuma Goto, Mikihiro Fujiya, Hiroaki Konishi, Junpei Sasajima, Shugo Fujibayashi, Akihiro Hayashi, Tatsuya Utsumi, Hiroki Sato, Takuya Iwama, Masami Ijiri, Aki Sakatani, Kazuyuki Tanaka, Yoshiki Nomura, Nobuhiro Ueno, Shin Kashima, Kentaro Moriichi, Yusuke Mizukami, Yutaka Kohgo, Toshikatsu Okumura
Format: Article
Language:English
Published: BMC 2018-01-01
Series:BMC Cancer
Subjects:
Online Access:http://link.springer.com/article/10.1186/s12885-018-4006-5
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author Takuma Goto
Mikihiro Fujiya
Hiroaki Konishi
Junpei Sasajima
Shugo Fujibayashi
Akihiro Hayashi
Tatsuya Utsumi
Hiroki Sato
Takuya Iwama
Masami Ijiri
Aki Sakatani
Kazuyuki Tanaka
Yoshiki Nomura
Nobuhiro Ueno
Shin Kashima
Kentaro Moriichi
Yusuke Mizukami
Yutaka Kohgo
Toshikatsu Okumura
author_facet Takuma Goto
Mikihiro Fujiya
Hiroaki Konishi
Junpei Sasajima
Shugo Fujibayashi
Akihiro Hayashi
Tatsuya Utsumi
Hiroki Sato
Takuya Iwama
Masami Ijiri
Aki Sakatani
Kazuyuki Tanaka
Yoshiki Nomura
Nobuhiro Ueno
Shin Kashima
Kentaro Moriichi
Yusuke Mizukami
Yutaka Kohgo
Toshikatsu Okumura
author_sort Takuma Goto
collection DOAJ
description Abstract Background Pancreatic cancer is associated with an extremely poor prognosis, so new biomarkers that can detect the initial stages are urgently needed. The significance of serum microRNA (miR) levels in pancreatic neoplasm such as pancreatic cancer and intraductal papillary mucinous neoplasm (IPMN) diagnosis remains unclear. We herein evaluated the usefulness of miRs enclosed in serum exosomes (ExmiRs) as diagnostic markers. Methods The ExmiRs from patients with pancreatic cancer (n = 32) or IPMN (n = 29), and patients without neoplasms (controls; n = 22) were enriched using ExoQuick-TC™. The expression of ExmiRs was evaluated using a next-generation sequencing analysis, and the selected three miRs through this analysis were confirmed by a quantitative real-time polymerase chain reaction. Results The expression of ExmiR-191, ExmiR-21 and ExmiR-451a was significantly up-regulated in patients with pancreatic cancer and IPMN compared to the controls (p < 0.05). A receiver operating characteristic curve analysis showed that the area under the curve and the diagnostic accuracy of ExmiRs were 5–20% superior to those of three serum bulky circulating miRs (e.g.; ExmiR-21: AUC 0.826, accuracy 80.8%. Circulating miR-21: AUC 0.653, accuracy 62.3%). In addition, high ExmiR-451a was associated with mural nodules in IPMN (p = 0.010), and high ExmiR-21 was identified as a candidate prognostic factor for the overall survival (p = 0.011, HR 4.071, median OS of high-ExmiR-21: 344 days, median OS of low-ExmiR-21: 846 days) and chemo-resistant markers (p = 0.022). Conclusions The level of three ExmiRs can thus serve as early diagnostic and progression markers of pancreatic cancer and IPMN, and considered more useful markers than the circulating miRs (limited to these three miRs).
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spelling doaj.art-189e5a9629a94836a90a61b3e38d93d42022-12-22T01:09:03ZengBMCBMC Cancer1471-24072018-01-0118111110.1186/s12885-018-4006-5An elevated expression of serum exosomal microRNA-191, − 21, −451a of pancreatic neoplasm is considered to be efficient diagnostic markerTakuma Goto0Mikihiro Fujiya1Hiroaki Konishi2Junpei Sasajima3Shugo Fujibayashi4Akihiro Hayashi5Tatsuya Utsumi6Hiroki Sato7Takuya Iwama8Masami Ijiri9Aki Sakatani10Kazuyuki Tanaka11Yoshiki Nomura12Nobuhiro Ueno13Shin Kashima14Kentaro Moriichi15Yusuke Mizukami16Yutaka Kohgo17Toshikatsu Okumura18Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical UniversityDivision of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical UniversityDivision of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical UniversityDivision of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical UniversityDivision of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical UniversityDivision of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical UniversityDivision of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical UniversityDivision of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical UniversityDivision of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical UniversityDivision of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical UniversityDivision of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical UniversityDivision of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical UniversityDivision of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical UniversityDivision of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical UniversityDivision of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical UniversityDivision of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical UniversityDivision of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical UniversityDepartment of Gastroenterology, International University of Health and Welfare HospitalDivision of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical UniversityAbstract Background Pancreatic cancer is associated with an extremely poor prognosis, so new biomarkers that can detect the initial stages are urgently needed. The significance of serum microRNA (miR) levels in pancreatic neoplasm such as pancreatic cancer and intraductal papillary mucinous neoplasm (IPMN) diagnosis remains unclear. We herein evaluated the usefulness of miRs enclosed in serum exosomes (ExmiRs) as diagnostic markers. Methods The ExmiRs from patients with pancreatic cancer (n = 32) or IPMN (n = 29), and patients without neoplasms (controls; n = 22) were enriched using ExoQuick-TC™. The expression of ExmiRs was evaluated using a next-generation sequencing analysis, and the selected three miRs through this analysis were confirmed by a quantitative real-time polymerase chain reaction. Results The expression of ExmiR-191, ExmiR-21 and ExmiR-451a was significantly up-regulated in patients with pancreatic cancer and IPMN compared to the controls (p < 0.05). A receiver operating characteristic curve analysis showed that the area under the curve and the diagnostic accuracy of ExmiRs were 5–20% superior to those of three serum bulky circulating miRs (e.g.; ExmiR-21: AUC 0.826, accuracy 80.8%. Circulating miR-21: AUC 0.653, accuracy 62.3%). In addition, high ExmiR-451a was associated with mural nodules in IPMN (p = 0.010), and high ExmiR-21 was identified as a candidate prognostic factor for the overall survival (p = 0.011, HR 4.071, median OS of high-ExmiR-21: 344 days, median OS of low-ExmiR-21: 846 days) and chemo-resistant markers (p = 0.022). Conclusions The level of three ExmiRs can thus serve as early diagnostic and progression markers of pancreatic cancer and IPMN, and considered more useful markers than the circulating miRs (limited to these three miRs).http://link.springer.com/article/10.1186/s12885-018-4006-5Pancreatic cancerExosomemicroRNA-21microRNA-451aIntraductal papillary mucinous neoplasmTumor marker
spellingShingle Takuma Goto
Mikihiro Fujiya
Hiroaki Konishi
Junpei Sasajima
Shugo Fujibayashi
Akihiro Hayashi
Tatsuya Utsumi
Hiroki Sato
Takuya Iwama
Masami Ijiri
Aki Sakatani
Kazuyuki Tanaka
Yoshiki Nomura
Nobuhiro Ueno
Shin Kashima
Kentaro Moriichi
Yusuke Mizukami
Yutaka Kohgo
Toshikatsu Okumura
An elevated expression of serum exosomal microRNA-191, − 21, −451a of pancreatic neoplasm is considered to be efficient diagnostic marker
BMC Cancer
Pancreatic cancer
Exosome
microRNA-21
microRNA-451a
Intraductal papillary mucinous neoplasm
Tumor marker
title An elevated expression of serum exosomal microRNA-191, − 21, −451a of pancreatic neoplasm is considered to be efficient diagnostic marker
title_full An elevated expression of serum exosomal microRNA-191, − 21, −451a of pancreatic neoplasm is considered to be efficient diagnostic marker
title_fullStr An elevated expression of serum exosomal microRNA-191, − 21, −451a of pancreatic neoplasm is considered to be efficient diagnostic marker
title_full_unstemmed An elevated expression of serum exosomal microRNA-191, − 21, −451a of pancreatic neoplasm is considered to be efficient diagnostic marker
title_short An elevated expression of serum exosomal microRNA-191, − 21, −451a of pancreatic neoplasm is considered to be efficient diagnostic marker
title_sort elevated expression of serum exosomal microrna 191 21 451a of pancreatic neoplasm is considered to be efficient diagnostic marker
topic Pancreatic cancer
Exosome
microRNA-21
microRNA-451a
Intraductal papillary mucinous neoplasm
Tumor marker
url http://link.springer.com/article/10.1186/s12885-018-4006-5
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