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01.12.2018 | Research article | Ausgabe 1/2018 Open Access

BMC Cancer 1/2018

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

Zeitschrift:
BMC Cancer > Ausgabe 1/2018
Autoren:
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
Wichtige Hinweise

Electronic supplementary material

The online version of this article (https://​doi.​org/​10.​1186/​s12885-018-4006-5) contains supplementary material, which is available to authorized users.

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).
Zusatzmaterial
Additional file 1: Table S1. The differences in the expression of exosomes between the IPMN and PC patients. An ELISA revealed no significant difference in the CD63 expression of exosomes in the serum samples, indicating that the expression of exosomes did not markedly differ among the groups (PC = 31, IPMN = 29, control = 20).
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