MiR-21-5p in urinary extracellular vesicles is a novel biomarker of urothelial carcinoma
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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
Kazutoshi Fujita, email: firstname.lastname@example.org
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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