Bladder cancer detection by urinary extracellular vesicle mRNA analysis
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Taku Murakami1, Cindy M. Yamamoto1, Tomoshige Akino2, Hiroshi Tanaka2, Nobuyuki Fukuzawa2, Hidetaka Suzuki2, Takahiro Osawa3, Takahiro Tsuji2, Toshimori Seki2 and Hiroshi Harada2
1Hitachi Chemical Co. America, Ltd., Irvine, CA, USA
2Sapporo City General Hospital, Sapporo, Japan
3Graduate School of Medicine, Hokkaido University, Sapporo, Japan
Taku Murakami, email: [email protected]
Keywords: bladder cancer; biomarker; extracellular vesicles; exosome; mRNA
Received: May 03, 2018 Accepted: August 04, 2018 Published: August 28, 2018
Objective: Urinary extracellular vesicles (EV) could be promising biomarkers for urological diseases. In this retrospective feasibility study, we conducted biomarker screening for early stage bladder cancer using EV mRNA analysis.
Methods: Biomarker candidates were identified through RNA-seq analysis of urinary EV from patients with non-muscle invasive bladder cancer (N=3), advanced urothelial cancer (N=3), no residual tumor after TURBT (N=2), and healthy and disease controls (N=4). Diagnostic performance was evaluated by RT-qPCR in a larger patient group including bladder cancer (N=173), renal pelvis and ureter cancer (N=33), no residual tumor and non-cancer disease control (N=36).
Results: Urinary EV SLC2A1, GPRC5A and KRT17 were overexpressed in pT1 and higher stage bladder cancer by 20.6-fold, 18.2-fold and 29.5-fold, respectively. These genes allowed detection of non-muscle invasive bladder cancer (AUC: 0.56 to 0.64 for pTa, 0.62 to 0.80 for pTis, and 0.82 to 0.86 for pT1) as well as pT2 and higher muscle invasive bladder cancer (AUC: 0.72 to 0.90). Subgroup analysis indicated that these markers could be useful for the detection of cytology-negative/-suspicious and recurrent bladder cancers.
Conclusion: Three urinary EV mRNA were discovered to be elevated in bladder cancer. Urinary EV mRNA are promising biomarkers of urothelial cancer and worth further investigation.
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