Research Papers:

MiR-21-5p in urinary extracellular vesicles is a novel biomarker of urothelial carcinoma

Kyosuke Matsuzaki, Kazutoshi Fujita, _ Kentaro Jingushi, Atsunari Kawashima, Takeshi Ujike, Akira Nagahara, Yuko Ueda, Go Tanigawa, Iwao Yoshioka, Koji Ueda, Rikinari Hanayama, Motohide Uemura, Yasushi Miyagawa, Kazutake Tsujikawa, Norio Nonomura

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Oncotarget. 2017; 8:24668-24678. https://doi.org/10.18632/oncotarget.14969

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Kyosuke Matsuzaki1, Kazutoshi Fujita1, Kentaro Jingushi2, Atsunari Kawashima1, Takeshi Ujike1, Akira Nagahara1, Yuko Ueda2, Go Tanigawa3, Iwao Yoshioka4, Koji Ueda5, Rikinari Hanayama6, Motohide Uemura1, Yasushi Miyagawa1, Kazutake Tsujikawa2, Norio Nonomura1

1Department of Urology, Osaka University Graduate School of Medicine, Osaka, Japan

2Laboratory of Molecular and Cellular Physiology, Osaka University Graduate School of Pharmaceutical Science, Osaka, Japan

3Department of Urology, Osaka General Medical Center, Osaka, Japan

4Department of Urology, Osaka Police Hospital, Osaka, Japan

5Cancer Proteomics Group, Genome Center, Japanese Foundation for Cancer Research, Tokyo, Japan

6Department of Immunology, Kanazawa University Graduate School of Medical Sciences, Ishikawa, Japan

Correspondence to:

Kazutoshi Fujita, email: kazufujita2@gmail.com

Keywords: extracellular vesicles, urothelial carcinoma, microRNA, urine, biomarker

Received: August 08, 2016    Accepted: January 10, 2017    Published: February 01, 2017


Background: Extracellular vesicles are lipid bilayer vesicles containing protein, messengerRNA and microRNA. Cancer cell-derived extracellular vesicles may be diagnostic and therapeutic targets. We extracted extracellular vesicles from urine of urothelial carcinoma patients and the control group to identify cancer-specific microRNAs in urinary extracellular vesicles as new biomarkers.

Materials and methods: microRNA from urinary extracellular vesicles extracted from 6 urothelial carcinoma patients and 3 healthy volunteers was analyzed. We verified candidate microRNAs in an independent cohort of 60 urinary extracellular vesicles samples. To normalize the microRNA expression level in extracellular vesicles, we examined the following in extracellular vesicles: protein concentration, CD9 intensity, amounts of whole miRNAs, RNA U6B small nuclear expression and the creatinine concentration of original urine correlating with the counts of extracted extracellular vesicles measured by the NanoSight™ system.

Results: From the microarray results 5 microRNAs overexpressed in urinary extracellular vesicles of urothelial carcinoma patients were identified. Creatinine concentration of original urine correlated most with particle counts of extracellular vesicles, indicating that creatinine could be a new tool for normalizing microRNA expression. MiR-21-5p was the most potent biomarker in urinary extracellular vesicles (sensitivity, 75.0%; specificity, 95.8%) and was also overexpressed in urinary extracellular vesicles from urothelial carcinoma patients with negative urine cytology. For the subgroup with negative urine cytology, the sensitivity was 75.0% and specificity was 95.8%.

Conclusion: MiR-21-5p in urinary extracellular vesicles could be a new biomarker of urothelial carcinoma, especially for urothelial carcinoma patients with negative urine cytology.

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