Abstract
ObjectiveUrinary 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.MethodsBiomarker 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).ResultsUrinary 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.ConclusionThree urinary EV mRNA were discovered to be elevated in bladder cancer. Urinary EV mRNA are promising biomarkers of urothelial cancer and worth further investigation.
Highlights
National Cancer Institute estimated that there will be approximately 74,000 new bladder cancer cases and 14,000 deaths in the United States alone [1]
Three urinary Extracellular vesicles (EV) mRNA were discovered to be elevated in bladder cancer
Urinary EV was obtained from patients with bladder cancer (BC, N=4), renal pelvis cancer (RPC, N=2), no residual tumor after transurethral resection of bladder tumor (TURBT) (NRT, N=2), and healthy (HC, N=3) and disease controls (DC, N=1) and applied to RNA-seq analysis (Table 1)
Summary
About 75% of bladder cancer is non-muscle-invasive cancer (Ta, Tis and T1) and about 25% is muscle-invasive cancer (T2, T3 and T4) [1]. Since the recurrence and progression rate is 50 to 70% for the non-muscle-invasive cancers, the patients with bladder cancer history require lifelong monitoring of recurrence, which makes bladder cancer the most expensive cancer from diagnosis to treatment in the US [2]. Other urothelial cancers located in ureters and renal pelvises are rare compared to bladder cancer, 20% to 50% of the patients will have bladder cancer in the future [3]. The recurrent nature of urothelial cancers demands non-invasive diagnostic tools for follow-up of patients. Current gold standard of bladder cancer detection is cystoscopy with urine cytology. Due to the invasiveness of cystoscopy, several urinary markers have been proposed none of the existing markers was validated yet to replace cystoscopy [1]
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