Urinary micro-RNA expressions and protein concentrations may differentiate bladder cancer patients from healthy controls

  • Gökçe Güllü Amuran
  • Ilker Tinay
  • Deniz Filinte
  • Can Ilgin
  • Irem Peker Eyüboğlu
  • Mustafa AkkiprikEmail author
Urology - Original Paper



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.


Bladder cancer Urinary protein Urine exosomal miRNA Urinary biomarker Bladder cancer diagnosis 



Bladder cancer


Non-muscle-invasive bladder cancer


Muscle-invasive bladder cancer


Low risk


High risk


Intermediate risk


Low-intermediate risk


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.

Ethical approval

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

Informed consent was obtained from all individual participants included in the study.

Supplementary material

11255_2019_2328_MOESM1_ESM.pdf (854 kb)
Supplementary material 1 (PDF 854 kb)


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Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  • Gökçe Güllü Amuran
    • 1
  • Ilker Tinay
    • 2
  • Deniz Filinte
    • 3
  • Can Ilgin
    • 4
  • Irem Peker Eyüboğlu
    • 1
  • Mustafa Akkiprik
    • 1
    Email author
  1. 1.Department of Medical Biology, School of MedicineMarmara UniversityIstanbulTurkey
  2. 2.Department of Urology, School of MedicineMarmara UniversityIstanbulTurkey
  3. 3.Department of Pathology, School of MedicineMarmara UniversityIstanbulTurkey
  4. 4.Department of Public Health, School of MedicineMarmara UniversityIstanbulTurkey

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