Investigation of miR-21, miR-141, and miR-221 in blood circulation of patients with prostate cancer (original) (raw)

Abstract

In addition to their potential as tissue-based markers for cancer classification and prognostication, the study of microRNAs (miRNAs) in blood circulation is also of interest. In the present study, we investigated the amounts of three cancer-related miRNAs, miR-21, -141, and -221 in blood plasma of prostate cancer (PCa) patients. A cohort of 51 patients with PCa was enrolled into the study, and miRNAs were measured in two subgroups, with localized/local advanced or metastatic PCa. A group of 20 healthy individuals served as the control group. miRNAs were quantified from the total RNA fraction using 200 μl plasma and the small RNA molecule RNU1A as a control for normalizing the miRNA amounts in circulation. We found similar levels of three miRNAs in healthy subjects with median values of 0.039, 0.033 and 0.04, respectively; (p = n.s.). In the patients, the miRNA levels were higher, with miR-21 being the highest (median, 1.51). The miR-221 levels were intermediate (median, 0.71) while the miR-141 displayed the lowest levels (median, 0.051). The differences between the control group and the patients were highly significant for the miR-21 (p < 0.001; area under the curve (AUC), 88%) and -221 (p < 0.001; AUC, 83%) but not for the miR-141 (p = 0.2). In patients diagnosed with metastatic PCa, levels of all three miRNAs were significantly higher than in patients with localized/local advanced disease where the difference for the miR-141 was most pronounced (p < 0.001; AUC, 75.5%). In conclusion, analysis of miR-21, -141, and -221 in blood of PCa patients reveals varying patterns of these molecules in clinical subgroups of PCa.

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References

  1. Hayat MJ, Howlader N, Reichman ME, Edwards BK. Cancer statistics, trends, and multiple primary cancer analyses from the Surveillance, Epidemiology, and End Results (SEER) Program. Oncologist. 2007;12:20–37.
    Article PubMed Google Scholar
  2. Sboner A, Demichelis F, Calza S, Pawitan Y, Setlur SR, Hoshida Y, et al. Molecular sampling of prostate cancer: a dilemma for predicting disease progression. BMC Med Genomics. 2010;3:8.
    Article PubMed Google Scholar
  3. Roberts WW, Bergstralh EJ, Blute ML, Slezak JM, Carducci M, Han M, et al. Contemporary identification of patients at high risk of early prostate cancer recurrence after radical retropubic prostatectomy. Urology. 2001;57:1033–37.
    Article PubMed CAS Google Scholar
  4. Ferracin M, Veronese A, Negrini M. Micromarkers: miRNAs in cancer diagnosis and prognosis. Expert Rev Mol Diagn. 2010;10:297–308.
    Article PubMed CAS Google Scholar
  5. Volinia S, Calin GA, Liu CG, Ambs S, Cimmino A, Petrocca F, et al. A microRNA expression signature of human solid tumors defines cancer gene targets. Proc Natl Acad Sci. 2006;103:2257–61.
    Article PubMed CAS Google Scholar
  6. Ambs S, Prueitt RL, Yi M, Hudson RS, Howe TM, Petrocca F, et al. Genomic profiling of microRNA and messenger RNA reveals deregulated microRNA expression in prostate cancer. Cancer Res. 2008;68:6162–70.
    Article PubMed CAS Google Scholar
  7. Porkka KP, Pfeiffer MJ, Waltering KK, Vessella RL, Tammela TL, Visakorpi T. MicroRNA expression profiling in prostate cancer. Cancer Res. 2007;67:6130–35.
    Article PubMed CAS Google Scholar
  8. Ozen M, Creighton CJ, Ozdemir M, Ittmann M. Widespread deregulation of microRNA expression in human prostate cancer. Oncogene. 2008;27:1788–93.
    Article PubMed CAS Google Scholar
  9. Schaefer A, Jung M, Kristiansen G, Lein M, Schrader M, Miller K, et al. MicroRNAs and cancer: current state and future perspectives in urologic oncology. Urol Oncol. 2010;28:4–13.
    Article PubMed CAS Google Scholar
  10. Mitchell PS, Parkin RK, Kroh EM, Fritz BR, Wyman SK, Pogosova-Agadjanyan EL, et al. Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci. 2008;105:10513–18.
    Article PubMed CAS Google Scholar
  11. Kosaka N, Iguchi H, Ochiya T. Circulating microRNA in body fluid: a new potential biomarker for cancer diagnosis and prognosis. Cancer Sci. 2010;10:2087–92.
    Article Google Scholar
  12. Lodes MJ, Caraballo M, Suciu D, Munro S, Kumar A, Anderson B. Detection of cancer with serum miRNAs on an oligonucleotide microarray. PLoS ONE. 2009;4:e6229.
    Article PubMed Google Scholar
  13. Tanaka M, Oikawa K, Takanashi M, Kudo M, Ohyashiki J, Ohyashiki K, et al. Down-regulation of miR-92 in human plasma is a novel marker for acute leukemia patients. PLoS ONE. 2009;4:e5532.
    Article PubMed Google Scholar
  14. Heneghan HM, Miller N, Kelly R, Newell J, Kerin MJ. Systemic miRNA-195 differentiates breast cancer from other malignancies and is a potential biomarker for detecting noninvasive and early stage disease. Oncologist. 2010;15:673–82.
    Article PubMed Google Scholar
  15. Brase JC, Johannes M, Schlomm T, Fälth M, Haese A, Steuber T, et al. Circulating miRNAs are correlated with tumor progression in prostate cancer. Int J Cancer. 2011;128:608–16.
    Article PubMed CAS Google Scholar
  16. Ribas J, Lupold SE. The transcriptional regulation of miR-21, its multiple transcripts, and their implication in prostate cancer. Cell Cycle. 2010;9:923–29.
    Article PubMed CAS Google Scholar
  17. Galardi S, Mercatelli N, Giorda E, Massalini S, Frajese GV, Ciafrè SA, et al. miR-221 and miR-222 expression affects the proliferation potential of human prostate carcinoma cell lines by targeting p27Kip1. J Biol Chem. 2007;282:23716–24.
    Article PubMed CAS Google Scholar
  18. Mercatelli N, Coppola V, Bonci D, Miele F, Costantini A, Guadagnoli M, et al. The inhibition of the highly expressed miR-221 and miR-222 impairs the growth of prostate carcinoma xenografts in mice. PLoS ONE. 2008;3:e4029.
    Article PubMed Google Scholar
  19. Umetani N, Hiramatsu S, Hoon DS. Higher amount of free circulating DNA in serum than in plasma is not mainly caused by contaminated extraneous DNA during separation. Ann NY Acad Sci. 2006;1075:299–307.
    Article PubMed CAS Google Scholar
  20. Baffa R, Fassan M, Volinia S, O’Hara B, Liu CG, Palazzo JP, et al. MicroRNA expression profiling of human metastatic cancers identifies cancer gene targets. J Pathol. 2009;219:214–21.
    Article PubMed CAS Google Scholar

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Acknowledgements

This work was supported by Istanbul University Research Fund (Project no. 7986).

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Authors and Affiliations

  1. Department of Radiation Oncology, Istanbul University Oncology Institute, 34390, Capa, Istanbul, Turkey
    Fulya Yaman Agaoglu, Yavuz Dizdar & Emin Darendeliler
  2. Department of Basic Oncology, Istanbul University Oncology Institute, 34390, Capa, Istanbul, Turkey
    Müge Kovancilar, Nejat Dalay & Ugur Gezer
  3. Department of Clinical Chemistry and Clinical Pharmacology, University of Bonn, Bonn, Germany
    Stefan Holdenrieder

Authors

  1. Fulya Yaman Agaoglu
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  2. Müge Kovancilar
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  3. Yavuz Dizdar
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  4. Emin Darendeliler
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  5. Stefan Holdenrieder
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  6. Nejat Dalay
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  7. Ugur Gezer
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Correspondence toUgur Gezer.

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Yaman Agaoglu, F., Kovancilar, M., Dizdar, Y. et al. Investigation of miR-21, miR-141, and miR-221 in blood circulation of patients with prostate cancer.Tumor Biol. 32, 583–588 (2011). https://doi.org/10.1007/s13277-011-0154-9

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