Abstract
BackgroundBladder cancer (BC) is one of the most common malignancies globally. Early diagnosis of it can significantly improve patients’ survival and quality of life. Urinary exosomes (UEs)-derived miRNAs might be a promising biomarker for BC detection.MethodA total of 12 patients with BC and 4 non-cancerous participants (as healthy control) were recruited from a single center between March 2018 and December 2019 as the discovery set. Midstream urine samples from each participants were collected and high-throughput sequencing and differentially expression analysis were conducted. Combined with miRNA expression profile of BC tissue from The Cancer Genome Atlas (TCGA), miRNAs biomarkers for BC were determined. Candidate miRNAs as biomarkers were selected followed by verification with a quantitative reverse-transcription polymerase chain reaction assay in an independent validation cohort consisting of 53 BC patients and 51 healthy controls. The receiver-operating characteristic (ROC) curve was established to evaluate the diagnostic performance of UE-derived miRNAs. The possible mechanism of miRNAs were revealed by bioinformatic analysis and explored in vitro experiments.ResultsWe identified that miR-93-5p, miR-516a-5p were simultaneously significantly increased both in UEs from BC compared with healthy control and BC tissue compared with normal tissue, which were verified by RT-qPCR in the validation cohort. Subsequently, the performance to discover BC of the miR-93-5p, miR-516a-5p was further verified with an area under ROC curve (AUC) of 0.838 and 0.790, respectively, which was significantly higher than that of urine cytology (AUC = 0.630). Moreover, miR-93-5p was significantly increased in muscle-invasive BC compared with non-muscle-invasive BC with an AUC of 0.769. Bioinformatic analysis revealed that B-cell translocation gene 2(BTG2) gene may be the hub target gene of miR-93-5p. In vitro experiments verified that miR-93-5p suppressed BTG2 expression and promoted BC cells proliferation, invasion and migration.ConclusionUrine derived exosomes have a distinct miRNA profile in BC patients, and urinary exosomal miRNAs could be used as a promising non-invasive tool to detect BC. In vitro experiments suggested that miR-93-5p overexpression may contribute to BC progression via suppressing BTG2 expression.
Highlights
Bladder cancer (BC) is one of the most common malignancies globally
We identified that miR-93-5p, miR-516a-5p were simultaneously significantly increased both in Urinary exosome (UE) from BC compared with healthy control and BC tissue compared with normal tissue, which were verified by RT-qPCR in the validation cohort
Urine derived exosomes have a distinct miRNA profile in BC patients, and urinary exosomal miRNAs could be used as a promising non-invasive tool to detect BC
Summary
Bladder cancer (BC) is one of the most common malignancies globally. Diagnosis of it can significantly improve patients’ survival and quality of life. NMIBC features a high recurrence rate and MIBC patients usually have a poor prognosis because of recurrence or metastasis [2, 3]. Pelvic recurrences usually carry a poor prognosis, despite treatment, with median survival from 4 to 8 months [4]. The poor prognosis of BC is partially due to lack of an effective non-invasive means for early screening. The invasiveness of cystoscopy limits its application as a regular screening tool for BC. Exploration of effective non-invasive biomarkers for screening BC can play a pivotal role in improving the prognosis and quality of lives of BC patients
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