Open Access

miR‑3940‑5p/miR‑8069 ratio in urine exosomes is a novel diagnostic biomarker for pancreatic ductal adenocarcinoma

  • Authors:
    • Naohiko Yoshizawa
    • Kazushi Sugimoto
    • Masahiko Tameda
    • Yuji Inagaki
    • Makoto Ikejiri
    • Hiroyuki Inoue
    • Masanobu Usui
    • Masaaki Ito
    • Yoshiyuki Takei
  • View Affiliations

  • Published online on: January 29, 2020     https://doi.org/10.3892/ol.2020.11357
  • Pages: 2677-2684
  • Copyright: © Yoshizawa et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Despite the development of several therapeutic options, the prognosis of pancreatic cancer remains poor. One reason for this is the difficulty of diagnosing the disease at an early stage. For example, carbohydrate antigen (CA) 19‑9, which is the most widely used biomarker for pancreatic cancer, cannot be used to detect the disease at early stages. Some studies have attempted to find novel biomarkers for pancreatic cancer. The aim of the present study was to find a novel diagnostic biomarker for pancreatic ductal adenocarcinoma (PDAC) in urine exosomes. Exosomes were isolated from urine and serum samples of patients with PDAC and control subjects, or culture media of cancer cell lines. MicroRNAs (miRNAs) were purified from exosomes. Novel biomarker candidates for PDCA were identisfied from urine exosome miRNA using expression profiling, and validated in a larger number of samples using 3D digital PCR. The results of a preliminary analysis of nine PDAC and seven control subjects revealed that the miR‑3940‑5p/miR‑8069 ratio in urine exosomes was elevated in the patients with PDAC. Experiments using cultured cancer cell lines revealed that the elevation of the miR‑3940‑5p/miR‑8069 ratio was specific for PDAC. Furthermore, the elevation of the miR‑3940‑5p/miR‑8069 ratio in exosomes tended to be higher in the urine than in the serum of patients with PDAC. Validation experiments on 43 PDAC, 12 chronic pancreatitis and 25 control subjects demonstrated that the miR‑3940‑5p/miR‑8069 ratio in urine exosomes was elevated in PDAC at a relatively early stage of the disease. When this ratio was used in combination with CA19‑9 for the diagnosis of PDAC, the sensitivity and positive predictive value improved to 93.0 and 78.4%, respectively, when either of them was positive. Additionally, the positive predictive value reached 100% when both were positive. The negative predictive value also improved to 89.7% when both were negative. The miR‑3940‑5p/miR‑8069 ratio in urine exosomes may be useful as a tool for the diagnosis of PDAC, particularly when used in combination with CA19‑9.
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April-2020
Volume 19 Issue 4

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Online ISSN:1792-1082

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Spandidos Publications style
Yoshizawa N, Sugimoto K, Tameda M, Inagaki Y, Ikejiri M, Inoue H, Usui M, Ito M and Takei Y: miR‑3940‑5p/miR‑8069 ratio in urine exosomes is a novel diagnostic biomarker for pancreatic ductal adenocarcinoma. Oncol Lett 19: 2677-2684, 2020
APA
Yoshizawa, N., Sugimoto, K., Tameda, M., Inagaki, Y., Ikejiri, M., Inoue, H. ... Takei, Y. (2020). miR‑3940‑5p/miR‑8069 ratio in urine exosomes is a novel diagnostic biomarker for pancreatic ductal adenocarcinoma. Oncology Letters, 19, 2677-2684. https://doi.org/10.3892/ol.2020.11357
MLA
Yoshizawa, N., Sugimoto, K., Tameda, M., Inagaki, Y., Ikejiri, M., Inoue, H., Usui, M., Ito, M., Takei, Y."miR‑3940‑5p/miR‑8069 ratio in urine exosomes is a novel diagnostic biomarker for pancreatic ductal adenocarcinoma". Oncology Letters 19.4 (2020): 2677-2684.
Chicago
Yoshizawa, N., Sugimoto, K., Tameda, M., Inagaki, Y., Ikejiri, M., Inoue, H., Usui, M., Ito, M., Takei, Y."miR‑3940‑5p/miR‑8069 ratio in urine exosomes is a novel diagnostic biomarker for pancreatic ductal adenocarcinoma". Oncology Letters 19, no. 4 (2020): 2677-2684. https://doi.org/10.3892/ol.2020.11357