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Cancer Sci. 2018 Nov 1. doi: 10.1111/cas.13856. [Epub ahead of print]

Circulating miRNA Panels for Specific and Early Detection in Bladder Cancer.

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Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.
Department of Urology, St.Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki-shi, Kanagawa, 216-8511, Japan.
Department of Urology, The Jikei University School of medicine, Minato-ku, Tokyo, Japan.
Toray Industries, Inc. 6-10-1 Tebiro, Kamakura city, Kanagawa, 248-0036, Japan.
Dynacom Co., Ltd, World Business Garden E25, 2-6-1 Nakase, Mihama-ku, Chiba city, Chiba, 261-7125, Japan.
Medical Genome Center, National Center for Geriatrics and Gerontology, 7-430 Morioka-cho, Obu, Aichi, 474-8511, Japan.
Department of Gastrointestinal Medical Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.
Department of Urology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.


Bladder cancer is the ninth leading cause of cancer death worldwide. The major problem in bladder cancer is primarily the high recurrence rate after drug treatment and resection. Although conventional screening methods, such as cystoscopy, urinary cytology and ultrasound sonography, have become widely used in a clinical setting, the diagnostic performance of these modalities is unsatisfactory due to low accuracy or high invasiveness. Since circulating miRNA profiles have recently been reported as an attractive tool for liquid biopsy in cancer screening, here, we performed global miRNA profiling of 392 serum samples of bladder cancer patient with 100 non-cancer samples and 480 samples of other types of cancer as controls. We randomly classified the bladder cancer and control samples into 2 cohorts, a training set (N = 486) and a validation set (N = 486). By comparing both controls, we identified specific miRNAs, such as miR-6087, for diagnosing bladder cancer in the training and validation sets. Furthermore, we found that a combination of 7 miRNAs (7-miRNA panel; miR-6087, miR-6724-5p, miR-3960, miR-1343-5p, miR-1185-1-3p, miR-6831-5p, and miR-4695-5p) could discriminate bladder cancer from non-cancer and other types of tumors with the highest accuracy (AUC: 0.97; sensitivity: 95%; specificity: 87%). The diagnostic accuracy was high, regardless of the stage and grade of bladder cancer. Our data demonstrated that the 7-miRNA panel could be a biomarker for the specific and early detection of bladder cancer. This article is protected by copyright. All rights reserved.


bladder cancer; circulating microRNA; diagnosis; early detection; liquid biopsy

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