Tumor Biology

, Volume 35, Issue 12, pp 12613–12617 | Cite as

Circulating miRNAs 21 and 221 as biomarkers for early diagnosis of prostate cancer

  • Sameh Kotb
  • Ashraf MosharafaEmail author
  • Mona Essawi
  • Heba Hassan
  • Alaa Meshref
  • Ahmed Morsy
Research Article


To compare the expression of two promising circulating micro-ribonucleic acids (miRNAs 21 and 221) in patients with prostate cancer to subjects without cancer and to evaluate their potential role as specific noninvasive molecular biomarkers for prostate cancer diagnosis, circulating miRNAs 21 and 221 expression profiles were analyzed in 20 men aged 50–75 years, presenting with lower urinary tract symptoms (LUTSs) and undergoing transrectal ultrasound (TRUS)-guided prostate biopsy based on either elevated serum prostate-specific antigen (PSA) (>4.0 ng/ml) or suspicious digital rectal examination (DRE). The performance of miRNAs 21 and 221 in differentiating prostate cancer from nonmalignant cases was evaluated and compared to DRE and elevated PSA. miRNA 21 was overexpressed in 90 % of group A vs. 10 % of group B, while miRNA 221 was overexpressed in 80 % of group A vs. 20 % of group B (p = 0.001). MiRNA 21 overexpression had the highest performance as a diagnostic test with a sensitivity of 90 % and a specificity 90 % (p = 0.02). No correlations were noted between Gleason score of prostate cancer cases and relative quantity (RQ) 21 (r = −0.355, p = 0.292) or RQ 221 (r = −0.044, p = 0.892). Our study showed that serum miRNAs 21 and 221 expression profiling tests may be used as specific noninvasive molecular biomarkers for prostate cancer diagnosis due to their higher sensitivity and specificity with a high negative predictive value leading to a decrease in the biopsies taken for patients with elevated serum PSA values.


miRNAs Prostate neoplasms Diagnosis Biological markers 


  1. 1.
    Porkka KP, Pfeiffer MJ, Waltering KK, et al. MicroRNA expression profiling in prostate cancer. Cancer Res. 2007;67:6130–5.PubMedCrossRefGoogle Scholar
  2. 2.
    Huang X, Liang M, Dittmar R, Wang L. Extracellular microRNAs in urologic malignancies: chances and challenges. Int J Mol Sci. 2013;14:14785–99.PubMedCentralPubMedCrossRefGoogle Scholar
  3. 3.
    Ribas J, Ni X, Haffner M, et al. miR-21: an androgen receptor-regulated microRNA that promotes hormone-dependent and hormone-independent prostate cancer growth. Cancer Res. 2009;69:7165–9.PubMedCentralPubMedCrossRefGoogle Scholar
  4. 4.
    Waltering K, Porkka K, Jalava S, Urbanucci A, Kohonen P, Latonen L, et al. Androgen regulation of micro-RNAs in prostate cancer. Prostate. 2011;71:604–14.PubMedCrossRefGoogle Scholar
  5. 5.
    Calin GA, Liu CG, Sevignani C, et al. MicroRNA profiling reveals distinct signatures in B cell chronic lymphocytic leukemias. Proc Natl Acad Sci U S A. 2004;101:11755–60.PubMedCentralPubMedCrossRefGoogle Scholar
  6. 6.
    Ma R, Jiang T, Kang X. Circulating microRNAs in cancer: origin, function and application. J Exp Clin Cancer Res. 2012;31:38.PubMedCentralPubMedCrossRefGoogle Scholar
  7. 7.
    Papagiannakopoulos T, Shapiro A, Kosik KS. MicroRNA-21 targets a network of key tumor-suppressive pathways in glioblastoma cells. Cancer Res. 2008;68:8164–72.PubMedCrossRefGoogle Scholar
  8. 8.
    Lu Z, Liu M, Stribinskis V, et al. MicroRNA-21 promotes cell transformation by targeting the programmed cell death 4 gene. Oncogene. 2008;27:4373–9.PubMedCrossRefGoogle Scholar
  9. 9.
    Liu LZ, Li C, Chen Q, Jing Y, Carpenter R, Jiang Y, et al. MiR-21 induced angiogenesis through AKT and ERK activation and HIF-1α expression. PLoS ONE. 2011;6(4):e19139. doi: 10.1371/journal.pone.0019139.PubMedCentralPubMedCrossRefGoogle Scholar
  10. 10.
    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(32):23716–24.PubMedCrossRefGoogle Scholar
  11. 11.
    Sun T, Wang Q, Balk S, Brown M, Lee GS, Kantoff P. The role of microRNA-221 and microRNA-222 in androgen-independent prostate cancer cell lines. Cancer Res. 2009;69:3356–63.PubMedCentralPubMedCrossRefGoogle Scholar
  12. 12.
    Reid G, Kirschner MB, van Zandwijk N. Circulating microRNAs: association with disease and potential use as biomarkers. Crit Rev Oncol Hematol. 2011;80:193–208.PubMedCrossRefGoogle Scholar
  13. 13.
    Brase JC, Johannes M, Schlomm T, et al. Circulating miRNAs are correlated with tumor progression in prostate cancer. lnt J Cancer. 2011;128:608–16.CrossRefGoogle Scholar
  14. 14.
    Mitchell PS, Parkin RK, Kroh EM, et al. Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci U S A. 2008;105:10513–8.PubMedCentralPubMedCrossRefGoogle Scholar
  15. 15.
    Moltzahn F, Olshen AB, Baehner L, et al. Microfluidic based multiplex qRT-PCR identifies diagnostic and prognostic microRNA signatures in sera of prostate cancer patients. Cancer Res. 2011;71:550.PubMedCentralPubMedCrossRefGoogle Scholar
  16. 16.
    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.PubMedCentralPubMedCrossRefGoogle Scholar
  17. 17.
    Chen ZH, Zhang GL, Li HR, Luo JD, Li ZX, Chen GM, et al. A panel of five circulating microRNAs as potential biomarkers for prostate cancer. Prostate. 2012;72:1443–52.PubMedCrossRefGoogle Scholar
  18. 18.
    Mahn R, Heukamp LC, Rogenhofer S, von Ruecker A, Muller SC, Ellinger J. Circulating microRNAs (miRNA) in serum of patients with prostate cancer. Urology. 2011;77:1265.e9–16.PubMedCrossRefGoogle Scholar
  19. 19.
    Zhang HL, Yang LF, Zhu Y, et al. Serum miRNA-21: elevated levels in patients with metastatic hormone-refractory prostate cancer and potential predictive factor for the efficacy of docetaxel-based chemotherapy. Prostate. 2011;71:326–31.PubMedCrossRefGoogle Scholar
  20. 20.
    Agaoglu FY, Kovancilar M, Dizdar Y, Darendeliler E, Holdenrieder S, Dalay N, et al. Investigation of miR-21, miR-141, and miR-221 in blood circulation of patients with prostate cancer. Tumor Biol. 2011;32:583–8.CrossRefGoogle Scholar
  21. 21.
    Shen J, Hruby GW, McKiernan JM, Gurvich I, Lipsky MJ, Benson MC, et al. Dysregulation of circulating microRNAs and prediction of aggressive prostate cancer. Prostate. 2012;72:1469–77.PubMedCentralPubMedCrossRefGoogle Scholar
  22. 22.
    Spahn M, Kneitz S, Scholz CJ, Stenger N, Rudiger T, Strobel P, et al. Expression of microRNA-221 is progressively reduced in aggressive prostate cancer and metastasis and predicts clinical recurrence. Int J Cancer. 2010;127(2):394–403.PubMedGoogle Scholar
  23. 23.
    Schaefer A, Jung M, Mollenkopf HJ, Wagner I, Stephan C, Jentzmik F, et al. Diagnostic and prognostic implications of microRNA profiling in prostate carcinoma. Int J Cancer. 2010;126(5):1166–76.PubMedGoogle Scholar
  24. 24.
    Kang SG, Ha YR, Kim SJ, et al. Do microRNA 96, 145 and 221 expressions really aid in the prognosis of prostate carcinoma. Asian J Androl. 2012;14:752–7.PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Sameh Kotb
    • 1
  • Ashraf Mosharafa
    • 1
    Email author
  • Mona Essawi
    • 2
  • Heba Hassan
    • 2
  • Alaa Meshref
    • 1
  • Ahmed Morsy
    • 1
  1. 1.Urology DepartmentCairo UniversityCairoEgypt
  2. 2.Medical Molecular Genetics DepartmentNational Research CentreCairoEgypt

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