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01.06.2011 | Original Article

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

verfasst von: Joana Heinzelmann, Brenda Henning, Jimsgene Sanjmyatav, Nicole Posorski, Thomas Steiner, Heiko Wunderlich, Mieczyslaw R. Gajda, Kerstin Junker

Erschienen in: World Journal of Urology | Ausgabe 3/2011

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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.

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 18:581–592PubMedCrossRef

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 181:125–143PubMed

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

Ljungberg B (2004) Prognostic factors in renal cell carcinoma. Urologe A 43(Suppl 3):S119–S120PubMed

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

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

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

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 136:855–862PubMedCrossRef

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 216:418–427PubMedCrossRef

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 75:835–841PubMedCrossRef

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 6:259–269PubMedCrossRef

13.

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

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 29:90PubMedCrossRef

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 105:5874–5878PubMedCrossRef

16.

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

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 104:15805–15810PubMedCrossRef

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 28:347–358PubMedCrossRef

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 64:3753–3756PubMedCrossRef

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 282:1479–1486PubMedCrossRef

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

Titel: Specific miRNA signatures are associated with metastasis and poor prognosis in clear cell renal cell carcinoma
verfasst von: Joana Heinzelmann
Brenda Henning
Jimsgene Sanjmyatav
Nicole Posorski
Thomas Steiner
Heiko Wunderlich
Mieczyslaw R. Gajda
Kerstin Junker
Publikationsdatum: 01.06.2011
Verlag: Springer-Verlag
Erschienen in: World Journal of Urology / Ausgabe 3/2011
Print ISSN: 0724-4983
Elektronische ISSN: 1433-8726
DOI: https://doi.org/10.1007/s00345-010-0633-4

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