Abstract
Urinary microRNAs (miRNAs) are potential biomarkers for the noninvasive diagnosis of bladder cancer (BC). In this study, we aimed to develop a urinary miRNAs panel for diagnosing and predicting recurrence of BC. Genome-wide miRNAs analysis by deep sequencing followed by two phases of quantitative real-time PCR assays were performed on urine supernatant of 276 BC patients and 276 controls. We identified a seven-miRNA panel (miR-7-5p, miR-22-3p, miR-29a-3p, miR-126-5p, miR-200a-3p, miR-375, and miR-423-5p) that provided high diagnostic accuracy of BC with an AUC of 0.923 and 0.916 in training and validation set, respectively. The corresponding AUCs of this panel for Ta, T1 and T2-T4 were 0.864, 0.930 and 0.978, significantly higher than those of urine cytology, which were 0.531, 0.628 and 0.724, respectively (all p < 0.05). Moreover, Kaplan–Meier analysis showed that nonmuscle-invasive BC (NMIBC) patients with high miR-22-3p and low miR-200a-3p level had worse recurrence-free survival (RFS) (p = 0.002 and 0.040, respectively). Multivariate Cox regression analysis revealed that miR-22-3p and miR-200a-3p were independently associated with RFS of NMIBC (p = 0.024 and 0.008, respectively). In conclusion, our results suggested that urinary miRNAs may have considerable clinical value in diagnosis and recurrence prediction of BC.
Highlights
Bladder cancer (BC) is one of the most common and lethal urological malignances worldwide
We identified the combination of let-7b-5p and miR-532-5p as the most suitable reference genes for urine miRNA detection by reverse transcription (RT)-qPCR
These findings suggest that urinary miRNAs obtained in a noninvasive manner may play important roles in the diagnosis and recurrence prediction of bladder cancer (BC)
Summary
Bladder cancer (BC) is one of the most common and lethal urological malignances worldwide. The incidence of BC has substantially increased over the last 10 years, and 74690 new cases were diagnosed [1]. The major problem of BC is the high recurrence rate and the recurrence of more than half of these cases can be observed within 5 years [2]. Voided urine cytology is non-invasive, but it has low sensitivity to diagnose low-grade BC. Many urine-based biomarkers such as nuclear matrix protein 22 (NMP22), bladder tumor antigen (BTA) and cytokeratin are still in the progression of continuous development during the past decades, but no one is ideal and cannot be recommended for large-scale cancer screening [3]. Novel biomarkers for diagnosing BC, especially at the early stage, and monitoring the recurrence of BC with high sensitivity and specificity should be explored
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