Urinary micro-RNA expressions and protein concentrations may differentiate bladder cancer patients from healthy controls
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To determine expression differences of urine exosomal miR-19b1-5p, 21-5p, 136-3p, 139-5p, 210-3p and concentration differences of urinary BLCA-4, NMP22, APE1/Ref1, CRK, VIM between bladder cancer, follow-up patients, and control samples, to evaluate diagnostic importance of these differences and establish a diagnostic panel for bladder cancer.
Urine samples of 59 bladder cancer patients, 34 healthy controls, and 12 follow-up patients without recurrence were enrolled to this study. Real-time PCR and ELISA were performed to determine urine exosomal miR-19b1-5p, 21-5p, 136-3p, 139-5p, 210-3p expressions and urinary BLCA-4, NMP22, APE1/Ref1, CRK, VIM, creatinine concentrations. Logistic regression analyses were performed to determine the diagnostic panel, the sensitivity, and specificity of the panel assessed by the ROC curve analysis. p values < 0.05 were considered statistically significant.
In bladder cancer risk groups, mir-139, -136, -19 and 210 expressions or positivity were found to be different and concentrations of urinary Ape1/Ref1, BLCA4, CRK, and VIM increased by twofold on average compared to healthy controls. Logistic regression and ROC analyses revealed that panel could differentiate bladder cancer patients from healthy controls with 80% sensitivity and 88% specificity (AUC = 0.899), low-risk patients from controls with 93% sensitivity and 95.5% specificity (AUC = 0.976). Despite the low number of samples, our findings suggest that urine exosomal miR-19b1-5p, 136-3p, 139-5p expression, and urinary APE1/Ref1, BLCA-4, CRK concentrations are promising candidates in terms of bladder cancer diagnosis.
Although our panel has great sensitivity for early detection of BC, it needs to be validated in larger populations.
KeywordsBladder cancer Urinary protein Urine exosomal miRNA Urinary biomarker Bladder cancer diagnosis
Non-muscle-invasive bladder cancer
Muscle-invasive bladder cancer
Food and drug administration
This study was funded by Marmara University Research Commission BAPKO-SAG-C-DRP-1310160441.
Compliance with ethical standards
Conflict of interest
The research was funded by Marmara University Research Commission BAPKO-SAG-C-DRP-1310160441.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional committee, reference number 09.2016.416 and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in the study.
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