Skip to main content

Advertisement

SpringerLink
Log in

Specific miRNA signatures are associated with metastasis and poor prognosis in clear cell renal cell carcinoma

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

Abstract

Purpose

MicroRNAs (miRNAs) play an important role as regulators of gene expression in tumourigenesis by controlling many biological processes in growth, development, differentiation and apoptosis. Previous studies have shown an altered expression of specific miRNAs in clear cell renal cell carcinoma (ccRCC). But the function in cancerogenesis and metastasis in this tumour type is almost unknown. We aimed at identifying specific miRNA expression patterns that are associated with metastasis and prognosis in ccRCC patients.

Methods

MiRNA of 30 human ccRCC including ten non-metastatic tumours, four tumours with metastasis after 3 years or later and four tumours with primary metastasis was isolated. We analysed the miRNA expression by using microarrays and qRT-PCR.

Results

We detected a miRNA signature that distinguishes between metastatic and non-metastatic ccRCC, including miR-451, miR-221, miR-30a, miR-10b and miR-29a. Furthermore, we identified a group of 12 miRNAs, such as let-7 family, miR-30c, miR-26a, which are decreased in highly aggressive primary metastatic tumours. We found also correlations between expression levels of specific miRNAs with progression-free survival and overall survival.

Conclusion

Our findings suggest that specific miRNAs are involved in metastasis and have an impact on the progression of the ccRCC. Furthermore, we identified specific miRNAs characterising very aggressive tumours with early metastasis. In addition, we determined candidate markers associated with survival of the patients. Thus, it seems possible to use miRNAs for prediction of progression to distant metastasis and prognosis analysing the primary tumour.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Ferlay J, Autier P, Boniol M, Heanue M, Colombet M, Boyle P (2007) Estimates of the cancer incidence and mortality in Europe in 2006. Ann Oncol 18:581–592

    Article  PubMed  CAS  Google Scholar 

  2. Thoenes W, Storkel S, Rumpelt HJ (1986) Histopathology and classification of renal cell tumors (adenomas, oncocytomas and carcinomas). The basic cytological and histopathological elements and their use for diagnostics. Pathol Res Pract 181:125–143

    PubMed  CAS  Google Scholar 

  3. Störkel S, van den Berg E (1995) Morphological classification of renal cancer. World J Urol 13:153–158

    Article  PubMed  Google Scholar 

  4. Ljungberg B (2004) Prognostic factors in renal cell carcinoma. Urologe A 43(Suppl 3):S119–S120

    PubMed  Google Scholar 

  5. Nicoloso MS, Spizzo R, Shimizu M, Rossi S, Calin GA (2009) MicroRNAs—the micro steering wheel of tumour metastases. Nat Rev Cancer 9:293–302

    Article  PubMed  CAS  Google Scholar 

  6. Bartel DP (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116:281–297

    Article  PubMed  CAS  Google Scholar 

  7. Croce CM, Calin GA (2005) miRNAs, cancer, and stem cell division. Cell 122:6–7

    Article  PubMed  CAS  Google Scholar 

  8. Yi Z, Fu Y, Zhao S, Zhang X, Ma C (2010) Differential expression of miRNA patterns in renal cell carcinoma and nontumorous tissues. J Cancer Res Clin Oncol 136:855–862

    Article  PubMed  CAS  Google Scholar 

  9. Nakada C, Matsuura K, Tsukamoto Y, Tanigawa M, Yoshimoto T, Narimatsu T, Nguyen LT, Hijiya N, Uchida T, Sato F et al (2008) Genome-wide microRNA expression profiling in renal cell carcinoma: significant down-regulation of miR-141 and miR-200c. J Pathol 216:418–427

    Article  PubMed  CAS  Google Scholar 

  10. Juan D, Alexe G, Antes T, Liu H, Madabhushi A, Delisi C, Ganesan S, Bhanot G, Liou LS (2009) Identification of a microRNA panel for clear-cell kidney cancer. Urology 75:835–841

    Article  PubMed  Google Scholar 

  11. Chow TF, Youssef YM, Lianidou E, Romaschin AD, Honey RJ, Stewart R, Pace KT, Yousef GM (2009) Differential expression profiling of microRNAs and their potential involvement in renal cell carcinoma pathogenesis. Clin Biochem (in press), Uncorrected proof

  12. Esquela-Kerscher A, Slack FJ (2006) Oncomirs [mdash] microRNAs with a role in cancer. Nat Rev Cancer 6:259–269

    Article  PubMed  CAS  Google Scholar 

  13. Calin GA, Croce CM (2006) MicroRNA signatures in human cancers. Nat Rev Cancer 6:857–866

    Article  PubMed  CAS  Google Scholar 

  14. Slaby O, Jancovicova J, Lakomy R, Svoboda M, Poprach A, Fabian P, Kren L, Michalek J, Vyzula R (2010) Expression of miRNA-106b in conventional renal cell carcinoma is a potential marker for prediction of early metastasis after nephrectomy. J Exp Clin Cancer Res 29:90

    Article  PubMed  Google Scholar 

  15. Sengupta S, den Boon JA, Chen IH, Newton MA, Stanhope SA, Cheng Y-J, Chen C-J, Hildesheim A, Sugden B, Ahlquist P (2008) MicroRNA 29c is down-regulated in nasopharyngeal carcinomas, up-regulating mRNAs encoding extracellular matrix proteins. Proc Natl Acad Sci 105:5874–5878

    Article  PubMed  CAS  Google Scholar 

  16. Ramaswamy S, Ross KN, Lander ES, Golub TR (2003) A molecular signature of metastasis in primary solid tumors. Nat Genet 33:49–54

    Article  PubMed  CAS  Google Scholar 

  17. Fabbri M, Garzon R, Cimmino A, Liu Z, Zanesi N, Callegari E, Liu S, Alder H, Costinean S, Fernandez-Cymering C et al (2007) MicroRNA-29 family reverts aberrant methylation in lung cancer by targeting DNA methyltransferases 3A and 3B. Proc Natl Acad Sci 104:15805–15810

    Article  PubMed  CAS  Google Scholar 

  18. Dangi-Garimella S, Yun J, Eves EM, Newman M, Erkeland SJ, Hammond SM, Minn AJ, Rosner MR (2009) Raf kinase inhibitory protein suppresses a metastasis signalling cascade involving LIN28 and let-7. EMBO J 28:347–358

    Article  PubMed  CAS  Google Scholar 

  19. Takamizawa J, Konishi H, Yanagisawa K, Tomida S, Osada H, Endoh H, Harano T, Yatabe Y, Nagino M, Nimura Y et al (2004) Reduced expression of the let-7 microRNAs in human lung cancers in association with shortened postoperative survival. Cancer Res 64:3753–3756

    Article  PubMed  CAS  Google Scholar 

  20. Scott GK, Goga A, Bhaumik D, Berger CE, Sullivan CS, Benz CC (2007) Coordinate suppression of ERBB2 and ERBB3 by enforced expression of micro-RNA miR-125a or miR-125b. J Biol Chem 282:1479–1486

    Article  PubMed  CAS  Google Scholar 

  21. Baffa R, Fassan M, Volinia S, O’Hara B, Liu CG, Palazzo JP, Gardiman M, Rugge M, Gomella LG, Croce CM, Rosenberg A (2009) MicroRNA expression profiling of human metastatic cancers identifies cancer gene targets. J Pathol 219:214–221

    Google Scholar 

Download references

Acknowledgments

We like to thank Franka Räck and Dr. Fabricio F. Costa for critically reading this manuscript.

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Urology, Jena University Hospital, Lessingstr.1, 07743, Jena, Germany

    Joana Heinzelmann, Brenda Henning, Jimsgene Sanjmyatav, Thomas Steiner, Heiko Wunderlich & Kerstin Junker

  2. Institute of Human Genetics and Anthropology, Core Unit Chip Application, Jena University Hospital, Jena, Germany

    Nicole Posorski

  3. Institute of Pathology, Jena University Hospital, Jena, Germany

    Mieczyslaw R. Gajda

Authors
  1. Joana Heinzelmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Brenda Henning
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jimsgene Sanjmyatav
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Nicole Posorski
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Thomas Steiner
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Heiko Wunderlich
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Mieczyslaw R. Gajda
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Kerstin Junker
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Joana Heinzelmann.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Heinzelmann, J., Henning, B., Sanjmyatav, J. et al. Specific miRNA signatures are associated with metastasis and poor prognosis in clear cell renal cell carcinoma. World J Urol 29, 367–373 (2011). https://doi.org/10.1007/s00345-010-0633-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00345-010-0633-4

Keywords

Search

Navigation