Skip to main content

Advertisement

Log in

Circulating microRNAs in serum: novel biomarkers for patients with bladder cancer?

  • Original Article
  • Published:
World Journal of Urology Aims and scope Submit manuscript

Abstract

Purpose

Recent studies indicate that circulating microRNAs in serum/plasma are a novel class of non-invasive biomarkers with diagnostic and prognostic information. So far, circulating microRNAs have not been analyzed in patients with bladder cancer.

Methods

We collected serum from patients with non-muscle invasive bladder cancer (NMIBC), muscle invasive bladder cancer (MIBC) and non-malignant urological disease. Total RNA was isolated from 400 μl of serum using the mirVana PARIS Kit; the artificial cel-miR-39 was spiked-in prior to RNA isolation to control different RNA isolation efficiencies. Quantitative real-time PCR was applied to measure the levels of 22 microRNAs upregulated in BCA tissue (miR-15a, miR-18a, miR-21, miR-93, miR-96, miR-103, miR-130b, miR-135b, miR-141, miR-182, miR-183, miR-190, miR-191, miR-200b, miR-422b, miR-425, miR-449b, miR-601, miR-639, miR-644, miR-649 and miR-1233) in the marker identification cohort (NMIBC, n = 11, MIBC, n = 10; controls, n = 10). The most promising serum microRNAs were tested in a validation cohort (NMIBC, n = 65, MIBC, n = 61; controls, n = 105).

Results

The RNA recovery was similar in patients with NMIBC, MIBC and control subjects. The analysis of serum microRNA levels in the marker identification cohort indicated that serum miR-141 and miR-639 levels were increased in bladder cancer patients compared to CTRL. The analysis of these miR-141 and miR-639 in the validation cohort demonstrated that microRNA levels were similar in bladder cancer patients and control subjects. Furthermore, microRNA levels were not correlated with clinicopathological parameters (pT-stage, metastasis, grading).

Conclusions

The analysis of serum miR-141 and miR-639 levels does not seem to be helpful in the diagnosis or prognosis of BCA.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D (2011) Global cancer statistics. CA Cancer J Clin 61:69–90

    Article  PubMed  Google Scholar 

  2. Lovat F, Valeri N, Croce CM (2011) MicroRNAs in the pathogenesis of cancer. Semin Oncol 38:724–733

    Article  CAS  PubMed  Google Scholar 

  3. Kosaka N, Iguchi H, Ochiya T (2010) Circulating microRNA in body fluid: a new potential biomarker for cancer diagnosis and prognosis. Cancer Sci 101:2087–2092

    Article  CAS  PubMed  Google Scholar 

  4. Lawrie CH, Gal S, Dunlop HM, Pushkaran B, Liggins AP, Pulford K et al (2008) Detection of elevated levels of tumour-associated microRNAs in serum of patients with diffuse large B-cell lymphoma. Br J Haematol 141:672–675

    Article  PubMed  Google Scholar 

  5. Zhao H, Shen J, Medico L, Wang D, Ambrosone CB, Liu S (2010) A pilot study of circulating miRNAs as potential biomarkers of early stage breast cancer. PLoS One 5:e13735

    Article  PubMed Central  PubMed  Google Scholar 

  6. Hu Z, Chen X, Zhao Y, Tian T, Jin G, Shu Y et al (2010) Serum microRNA signatures identified in a genome-wide serum microRNA expression profiling predict survival of non-small-cell lung cancer. J Clin Oncol 28:1721–1726

    Article  PubMed  Google Scholar 

  7. Mahn R, Heukamp LC, Rogenhofer S, von Ruecker A, Muller SC, Ellinger J (2011) Circulating microRNAs (miRNA) in serum of patients With prostate cancer. Urology 77:1265

    Article  PubMed  Google Scholar 

  8. Wulfken LM, Moritz R, Ohlmann C, Holdenrieder S, Jung V, Becker F et al (2011) MicroRNAs in renal cell carcinoma: diagnostic implications of serum miR-1233 levels. PLoS One 6:e25787

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  9. Gottardo F, Liu CG, Ferracin M, Calin GA, Fassan M, Bassi P et al (2007) Micro-RNA profiling in kidney and bladder cancers. Urol Oncol 25:387–392

    Article  CAS  PubMed  Google Scholar 

  10. Baffa R, Fassan M, Volinia S, O’Hara B, Liu CG, Palazzo JP et al (2009) MicroRNA expression profiling of human metastatic cancers identifies cancer gene targets. J Pathol 219:214–221

    Article  CAS  PubMed  Google Scholar 

  11. Catto JW, Miah S, Owen HC, Bryant H, Myers K, Dudziec E et al (2009) Distinct microRNA alterations characterize high- and low-grade bladder cancer. Cancer Res 69:8472–8481

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  12. Han Y, Chen J, Zhao X, Liang C, Wang Y, Sun L et al (2011) MicroRNA expression signatures of bladder cancer revealed by deep sequencing. PLoS One 6:e18286

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  13. Veerla S, Lindgren D, Kvist A, Frigyesi A, Staaf J, Persson H et al (2009) MiRNA expression in urothelial carcinomas: important roles of miR-10a, miR-222, miR-125b, miR-7 and miR-452 for tumor stage and metastasis, and frequent homozygous losses of miR-31. Int J Cancer 124:2236–2242

    Article  CAS  PubMed  Google Scholar 

  14. Dyrskjot L, Ostenfeld MS, Bramsen JB, Silahtaroglu AN, Lamy P, Ramanathan R et al (2009) Genomic profiling of microRNAs in bladder cancer: miR-129 is associated with poor outcome and promotes cell death in vitro. Cancer Res 69:4851–4860

    Article  CAS  PubMed  Google Scholar 

  15. Neely LA, Rieger-Christ KM, Neto BS, Eroshkin A, Garver J, Patel S et al (2010) A microRNA expression ratio defining the invasive phenotype in bladder tumors. Urol Oncol 28:39–48

    Article  CAS  PubMed  Google Scholar 

  16. Ichimi T, Enokida H, Okuno Y, Kunimoto R, Chiyomaru T, Kawamoto K et al (2009) Identification of novel microRNA targets based on microRNA signatures in bladder cancer. Int J Cancer 125:345–352

    Article  CAS  PubMed  Google Scholar 

  17. Song T, Xia W, Shao N, Zhang X, Wang C, Wu Y, et al (2010) Differential miRNA expression profiles in bladder urothelial carcinomas. Asian Pac J Cancer Prev 11(1513–7368 (Print)):905–911

    Google Scholar 

  18. Wang G, Zhang H, He H, Tong W, Wang B, Liao G et al (2010) Up-regulation of microRNA in bladder tumor tissue is not common. Int Urol Nephrol 42:95–102

    Article  PubMed  Google Scholar 

  19. Mitchell PS, Parkin RK, Kroh EM, Fritz BR, Wyman SK, Pogosova-Agadjanyan EL et al (2008) Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci USA 105:10513–10518

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  20. Brase JC, Johannes M, Schlomm T, Falth M, Haese A, Steuber T et al (2011) Circulating miRNAs are correlated with tumor progression in prostate cancer. Int J Cancer 128:608–616

    Article  CAS  PubMed  Google Scholar 

  21. Gonzales JC, Fink LM, Goodman OB, Symanowski JT, Vogelzang NJ, Ward DC (2011) Comparison of circulating MicroRNA 141 to circulating tumor cells, lactate dehydrogenase, and prostate-specific antigen for determining treatment response in patients with metastatic prostate cancer. Clin Genitourin Cancer 9:39–45

    Article  PubMed  Google Scholar 

  22. Cheng H, Zhang L, Cogdell DE, Zheng H, Schetter AJ, Nykter M et al (2011) Circulating plasma MiR-141 is a novel biomarker for metastatic colon cancer and predicts poor prognosis. PLoS One 6:e17745

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  23. Liu X-G, Zhu W-Y, Huang Y–Y, Ma L-N, Zhou S-Q, Wang Y-K et al (2012) High expression of serum miR-21 and tumor miR-200c associated with poor prognosis in patients with lung cancer. Med Oncol 29:618–626

    Article  CAS  PubMed  Google Scholar 

  24. Hu M, Xia M, Chen X, Lin Z, Xu Y, Ma Y et al (2012) MicroRNA-141 regulates Smad interacting protein 1 (SIP1) and inhibits migration and invasion of colorectal cancer cells. Dig Dis Sci 55:2365–2372

    Article  Google Scholar 

  25. Imanaka Y, Tsuchiya S, Sato F, Shimada Y, Shimizu K, Tsujimoto G (2011) MicroRNA-141 confers resistance to cisplatin-induced apoptosis by targeting YAP1 in human esophageal squamous cell carcinoma. J Hum Genet 56:270–276

    Article  CAS  PubMed  Google Scholar 

  26. Wang G, Chan ES-Y, Kwan BC-H, Li PK-T, Yip SK-H, Szeto C–C et al (2012) Expression of microRNAs in the Urine of Patients With Bladder Cancer. Clin Genitourin Cancer 10:106–113

    Article  PubMed  Google Scholar 

  27. Sanders I, Holdenrieder S, Walgenbach-Brünagel G, von Rücker A, Kristiansen G, Müller SC, et al Evaluation of reference genes for the analysis fo serum miRNA in patients with prostate cancer, bladder cancer and renal cell carcinoma. Int J Urol (in press) (doi: 10.1111/j.1442-2042.2012.03082.x)

Download references

Acknowledgments

The study was supported by a research grant to Jörg Ellinger from the Deutsche Forschungsgemeinschaft (EL-623/1-1). The collection of serum samples was performed within the framework of the Biobank of the CIO Köln/Bonn.

Conflict of interest

The authors disclose any conflict of interest.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Jörg Ellinger.

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Cite this article

Scheffer, AR., Holdenrieder, S., Kristiansen, G. et al. Circulating microRNAs in serum: novel biomarkers for patients with bladder cancer?. World J Urol 32, 353–358 (2014). https://doi.org/10.1007/s00345-012-1010-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00345-012-1010-2

Keywords

Navigation