Genome-wide identification of urinary cell-free microRNAs for non-invasive detection of bladder cancer
Language English Country Great Britain, England Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
29363887
PubMed Central
PMC5824364
DOI
10.1111/jcmm.13487
Knihovny.cz E-resources
- Keywords
- biomarker, bladder cancer, cell-free miRNAs, non-invasive diagnosis, urine,
- MeSH
- Genome-Wide Association Study MeSH
- Adult MeSH
- Genome, Human MeSH
- Carcinoma diagnosis genetics pathology urine MeSH
- Middle Aged MeSH
- Humans MeSH
- MicroRNAs genetics urine MeSH
- Biomarkers, Tumor genetics urine MeSH
- Urinary Bladder Neoplasms diagnosis genetics pathology urine MeSH
- Prospective Studies MeSH
- Gene Expression Regulation, Neoplastic * MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Case-Control Studies MeSH
- Neoplasm Grading MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- MicroRNAs MeSH
- MIRN191 microRNA, human MeSH Browser
- MIRN31 microRNA, human MeSH Browser
- MIRN93 microRNA, human MeSH Browser
- Biomarkers, Tumor MeSH
Urinary microRNAs (miRNAs) are emerging as clinically useful tool for early and non-invasive detection of various types of cancer including bladder cancer (BCA). In this study, 205 patients with BCA and 99 healthy controls were prospectively enrolled. Expression profiles of urinary miRNAs were obtained using Affymetrix miRNA microarrays (2578 miRNAs) and candidate miRNAs further validated in independent cohorts using qRT-PCR. Whole-genome profiling identified 76 miRNAs with significantly different concentrations in urine of BCA compared to controls (P < 0.01). In the training and independent validation phase of the study, miR-31-5p, miR-93-5p and miR-191-5p were confirmed to have significantly higher levels in urine of patients with BCA in comparison with controls (P < 0.01). We further established 2-miRNA-based urinary DxScore (miR-93-5p, miR-31-5p) enabling sensitive BCA detection with AUC being 0.84 and 0.81 in the training and validation phase, respectively. Moreover, DxScore significantly differed in the various histopathological subgroups of BCA and decreased post-operatively. In conclusion, we identified and independently validated cell-free urinary miRNAs as promising biomarkers enabling non-invasive detection of BCA.
Central European Institute of Technology Masaryk University Brno Czech Republic
Department of Comprehensive Cancer Care Masaryk Memorial Cancer Institute Brno Czech Republic
Department of Urologic Oncology Masaryk Memorial Cancer Institute Brno Czech Republic
Department of Urology University Hospital Brno Masaryk University Brno Brno Czech Republic
See more in PubMed
Antoni S, Ferlay J, Soerjomataram I, et al Bladder cancer incidence and mortality: a global overview and recent trends. Eur Urol. 2017; 71: 96–108. PubMed
Goodison S, Rosser C, Urquidi V. Bladder cancer detection and monitoring: assessment of urine‐ and blood‐based marker tests. Mol Diagn Ther. 2013; 17: 71–84. PubMed PMC
Raitanen MP, Aine R, Rintala E, et al Differences between local and review urinary cytology in diagnosis of bladder cancer. An interobserver multicenter analysis. Eur Urol. 2002; 41: 284–9. PubMed
Boman H, Hedelin H, Holmäng S. Four bladder tumor markers have a disappointingly low sensitivity for small size and low grade recurrence. J Urol. 2002; 167: 80–3. PubMed
Enokida H, Yoshino H, Matsushita R, et al The role of microRNAs in bladder cancer. Investig Clin Urol. 2016; 57: S60. PubMed PMC
Weber JA, Baxter DH, Zhang S, et al The microRNA spectrum in 12 body fluids. Clin Chem. 2010; 56: 1733–41. PubMed PMC
Mlcochova H, Hezova R, Stanik M, et al Urine microRNAs as potential noninvasive biomarkers in urologic cancers. Urol Oncol. 2014; 32: 41. e1‐41.e9. PubMed
R Core Team . R: a language and environment for statistical computing. Vienna, Austria: R Foundation for Statistical Computing; 2014. http://www.R-project.org/.
Fedorko M, Juracek J, Stanik M, et al Detection of let‐7 miRNAs in urine supernatant as potential diagnostic approach in non‐metastatic clear‐cell renal cell carcinoma. Biochem Med (Zagreb). 2017; 27: 411–7. PubMed PMC
Hanke M, Hoefig K, Merz H, et al A robust methodology to study urine microRNA as tumor marker: microRNA‐126 and microRNA‐182 are related to urinary bladder cancer. Urol Oncol. 2010; 28: 655–61. PubMed
Wang G, Chan E, Kwan B, et al Expression of microRNAs in the urine of patients with bladder cancer. Clin Genitourin Cancer. 2012; 10: 106–13. PubMed
Puerta‐Gil P, García‐Baquero R, Jia AY, et al miR‐143, miR‐222, and miR‐452 are useful as tumor stratification and noninvasive diagnostic biomarkers for bladder cancer. Am J Pathol. 2012; 180: 1808–15. PubMed
Pospisilova S, Pazourkova E, Horinek A, et al MicroRNAs in urine supernatant as potential non‐invasive markers for bladder cancer detection. Neoplasma. 2016; 63: 799–808. PubMed
Urquidi V, Netherton M, Gomes‐Giacoia E, et al A microRNA biomarker panel for the non‐invasive detection of bladder cancer. Oncotarget. 2016; 7: 86290–9. PubMed PMC
Yun S, Jeong P, Kim W, et al Cell‐free microRNAs in urine as diagnostic and prognostic biomarkers of bladder cancer. Int J Oncol. 2012; 41: 1871–8. PubMed
De Long J, Sullivan T, Humphrey J, et al A non‐invasive miRNA based assay to detect bladder cancer in cell‐free urine. Am J Transl Res. 2015; 7: 2500–9. PubMed PMC
Yamada Y, Enokida H, Kojima S, et al MiR‐96 and miR‐183 detection in urine serve as potential tumor markers of urothelial carcinoma: correlation with stage and grade, and comparison with urinary cytology. Cancer Sci. 2011; 102: 522–9. PubMed
Robertson AG, Kim J, Al‐Ahmadie H, et al Comprehensive molecular characterization of muscle‐invasive bladder cancer. Cell. 2017; 171: 540–56. pii: S0092‐8674 (17) 31056‐5. PubMed PMC
Cell-free microRNAs as Non-invasive Diagnostic and Prognostic Bio- markers in Pancreatic Cancer