Abstract
Bladder cancer (BC) is currently diagnosed and monitored by cystoscopy, a costly and invasive procedure. Potential biomarkers in urine, blood, and, more recently, extracellular vesicles (EVs), have been explored as non-invasive alternatives for diagnosis and surveillance of BC. EVs are nanovesicles secreted by most cell types containing diverse molecular cargo, including different types of small RNAs, such as microRNA (miRNA). In this study, we performed next-generation sequencing of EV-contained miRNA isolated from urine and serum of 41 patients with non-muscle invasive BC (27 stage Ta, 14 stage T1) and 15 non-cancer patients (NCP) with benign cystoscopy findings. MiRNA sequencing was also performed on serum supernatant samples for T1 patients. To identify potential BC-specific biomarkers, expression levels of miRNA in presurgery samples were compared to those at postsurgery check-ups, and to NCPs. Results showed that two miRNAs, urinary EV-contained miR-451a and miR-486-5p, were significantly upregulated in presurgery samples from T1 patients compared to postsurgery check-up samples. This was confirmed in a replica EV/RNA isolation and sequencing run of 10 T1 patients from the primary run; however, analyses revealed no differential expression of miRNAs in serum EVs, serum supernatant, or when comparing BC patients to NCPs. This is the first study to investigate EV-containing miRNA sequencing in pre- and postsurgery BC patient samples and our findings suggest that urinary EV-contained miR-451a and miR-486-5p may be potential biomarkers for recurrence-free survival of BC patients with stage T1 disease.
Highlights
Bladder cancer (BC) is the second most common urological cancer with more than500,000 new cases annually worldwide [1]
Serum and urine samples were collected from 41 BC patients and 15 non-cancer patients (NCP) fulfilling the study inclusion criteria
A larger sample size would be advantageous to solidify our findings, this study suggests that miR-451a and miR-486-5p may be potential biomarkers for recurrence-free survival of BC patients with stage T1 disease
Summary
Bladder cancer (BC) is the second most common urological cancer with more than500,000 new cases annually worldwide [1]. Microvesicles (MVs) are more heterogeneous in size, (100–1000 nm in diameter), and are secreted through a budding process of the plasma membrane [9,10]. Both types of EVs consist of a lipid bilayer enveloping diverse types of intravesicular cargo such as peptides, metabolites, and RNA, including small RNAs (sRNA) such as microRNA miRNA [11,12,13]. As the intravesicular molecular cargo is protected from degradation, EVs isolated from bodily fluids such as urine and serum are considered promising reservoirs of biomarkers for various cancers, including BC [16,17,18]
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