Skip to main content

Advertisement

Log in

Serum microRNA-21 expression as a prognostic and therapeutic biomarker for breast cancer patients

  • Original Article
  • Published:
Tumor Biology

Abstract

MiRNA-21 is recognized as the main active candidate and high expression in many solid tumors consequential cell proliferation, differentiation, apoptosis, and closely related to metastasis of disease. The study aimed to evaluate the serum miRNA-21 expression and therapy outcome in breast cancer patients and cell lines. Seventy-five histopathologically confirmed newly diagnosed breast cancer patients were included in the study; before and after therapy, patient’s blood sample were collected and analyzed for serum microRNA-21 expression by quantitative real-time PCR. In patients, 8.9 mean fold increased microRNA-21 expression was observed compared to controls. Increased expression was found to be associated with advanced stage (11.72-fold), lymph node involvement (11.12-fold), and distant metastases (20.17-fold). After treatment significant decrease in miRNA-21 expression was observed and found to be significant (p < 0.0001). Patients treated with neoadjuvant therapy had significant impact on miRNA-21 suppression and found to be significantly associated with different clinicopathological features of patients. Increased miRNA-21 expression was also found to be significantly associated with poor survival of breast cancer patients (p = 0.002). MicroRNA-21 expression could be used as promising predictive indicators for breast cancer prognosis. MicroRNA-21 over-expression was associated with response to neoadjuvant therapy and may perhaps be considered as primary treatment choice.

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
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Flynt AS, Lai EC. Biological principles of microRNA-mediated regulation: shared themes amid diversity. Nat Rev Genet. 2008;9:831–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. 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 U S A. 2008;105:10513–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Meng F, Henson R, Wehbe-Janek H, Ghoshal K, Jacob ST, Patel T. MicroRNA- 21 regulates expression of the PTEN tumor suppressor gene in human hepatocellular cancer. Gastroenterology. 2007;133:647–58.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Asangani IA, Rasheed SA, Nikolova DA, Leupold JH, Colburn NH, Post S, et al. MicroRNA-21 (miR-21) post-transcriptionally downregulates tumor suppressor Pdcd4 and stimulates invasion, intravasation and metastasis in colorectal cancer. Oncogene. 2008;27:2128–36.

    Article  CAS  PubMed  Google Scholar 

  5. 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.

    Article  CAS  PubMed  Google Scholar 

  6. Iorio MV, Ferracin M, Liu CG, Veronese A, Spizzo R, Sabbioni S, et al. MicroRNA gene expression deregulation in human breast cancer. Cancer Res. 2005;65:7065–70.

    Article  CAS  PubMed  Google Scholar 

  7. Luo X, Burwinkel B, Tao S, Brenner H. MicroRNA signatures: novel biomarker for colorectal cancer? Cancer Epidemiol Biomarkers Prev. 2011;20(7):1272–86.

    Article  CAS  PubMed  Google Scholar 

  8. Skrzypski M, Dziadziuszko R, Jassem J. MicroRNA in lung cancer diagnostics and treatment. Mutat Res. 2011;717(1–2):25–31.

    Article  CAS  PubMed  Google Scholar 

  9. Zhao L, Chen X, Cao Y. New role of microRNA: carcinogenesis and clinical application in cancer. Acta Biochim Biophys Sin Shanghai. 2011;43(11):831–9.

    Article  CAS  PubMed  Google Scholar 

  10. Moore LM, Zhang W. Targeting miR-21 in glioma: a small RNA with big potential. Expert Opin Ther Targets. 2010;14(11):1247–57.

    Article  CAS  PubMed  Google Scholar 

  11. Selcuklu SD, Donoghue MT, Spillane C. miR-21 as a key regulator of oncogenic processes. Biochem Soc Trans. 2009;37(Pt 4):918–25.

    Article  CAS  PubMed  Google Scholar 

  12. Krichevsky AM, Gabriely G. miR-21: a small multi-faceted RNA. J Cell Mol Med. 2009;13(1):39–53.

    Article  CAS  PubMed  Google Scholar 

  13. Rossi S, Shimizu M, Barbarotto E, Nicoloso MS, Dimitri F, Sampath D, et al. microRNA fingerprinting of CLL patients with chromosome 17p deletion identify a miR-21 score that stratifies early survival. Blood. 2010;116(6):945–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Tang J, Ahmad A, Sarkar FH. The role of microRNAs in breast cancer migration, invasion and metastasis. Int J Mol Sci. 2012;13:13414–37.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Corcoran C, Friel AM, Duffy MJ, Crown J, O’Driscoll L. Intracellular and extracellular microRNAs in breast cancer. Clin Chem. 2011;57:18–32.

    Article  CAS  PubMed  Google Scholar 

  16. Mei M, Ren Y, Zhou X, Yuan XB, Han L, Wang GX, et al. Downregulation of miR-21 enhances chemotherapeutic effect of taxol in breast carcinoma cells. Technol Cancer Res Treat. 2010;9:77–86.

    Article  CAS  PubMed  Google Scholar 

  17. Chen L, Bourguignon LY. Hyaluronan-CD44 interaction promotes c-Jun signaling and miRNA21 expression leading to Bcl-2 expression and chemoresistance in breast cancer cells. Mol Cancer. 2014;13:52.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Dong J, Zhao YP, Zhou L, Zhang TP, Chen G. Bcl-2 upregulation induced by miR-21 via a direct interaction is associated with apoptosis and chemoresistance in MIA PaCa-2 pancreatic cancer cells. Arch Med Res. 2011;42:8–14.

    Article  CAS  PubMed  Google Scholar 

  19. Fu X, Han Y, Wu Y, Zhu X, Lu X, Mao F, et al. Prognostic role of microRNA-21 in various carcinomas: a systematic review and meta-analysis. Eur J ClinInvest. 2011;41(11):1245–53. doi:10.1111/j.1365-2362.2011.02535.x7.

    Article  CAS  Google Scholar 

  20. Kumarswamy R, Volkmann I, Thum T. Regulation and function of miRNA-21 in health and disease. RNA Biol. 2011;8(5):706–13. doi:10.4161/rna.8.5.16154.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Mishra PJ, Merlino G. MicroRNA reexpression as differentiation therapy in cancer. J Clin Invest. 2009;119:2119–23.

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Chen X, Ba Y, Ma L, et al. Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases. Cell Res. 2008;18:997–1006.

    Article  CAS  PubMed  Google Scholar 

  23. Asaga S, Kuo C, Nguyen T, Terpenning M, Giuliano AE, Hoon DS. Direct serum assay for microRNA-21 concentrations in early and advanced breast cancer. Clin Chem. 2011;57:84–91.

    Article  CAS  PubMed  Google Scholar 

  24. Wang ZX, Bian HB, Wang JR, Cheng ZX, Wang KM, De W. Prognostic significance of serum miRNA-21 expression in human non-small cell lung cancer. J Surg Oncol. 2011;104:847–51.

    Article  CAS  PubMed  Google Scholar 

  25. Si H, Sun X, Chen Y, Cao Y, Chen S, Wang H, et al. Circulating microRNA-92a and microRNA-21 as novel minimally invasive biomarkers for primary breast cancer. J Cancer Res Clin Oncol. 2013;139(2):223–9.

    Article  CAS  PubMed  Google Scholar 

  26. Ng EK, Li R, Shin VY, Jin HC, Leung CP, Ma ES, et al. Circulating microRNAs as specific biomarkers for breast cancer detection. PLoS One. 2013;8(1), e53141.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Sempere LF, Kauppinen S. In: Bradshaw RA, Dennis EA, editors. Translational implications of microRNAs in clinical diagnostics and therapeutics: handbook of cell signaling. Oxford: Academic; 2009. p. 2965–e2981.

    Google Scholar 

  28. Schwartz GF, Hortobagyi GN, Masood S, Palazzo J, Holland R, Page D. Proceedings of the consensus conference on neoadjuvant chemotherapy in carcinoma of the breast, April 26–28, 2003, Philadelphia, PA. Hum Pathol. 2004;35:781–4.

    Article  PubMed  Google Scholar 

  29. Kaufmann M, von Minckwitz G, Bear HD, Buzdar A, McGale P, Bonnefoi H, et al. Recommendations from an international expert panel on the use of neoadjuvant (primary) systemic treatment of operable breast cancer: new perspectives 2006. Ann Oncol. 2007;18:1927–34.

    Article  CAS  PubMed  Google Scholar 

  30. Chia S, Swain SM, Byrd DR, Mankoff DA. Locally advanced and inflammatory breast cancer. J Clin Oncol. 2008;26:786–90.

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

The authors thank all the study subjects who were part of this study.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Alpana Saxena.

Ethics declarations

The study was approved by Institutional Ethics Committee, Maulana Azad Medical College, New Delhi. Written informed consent was obtained from all participants.

Conflicts of interest

None.

Additional information

Prasant Yadav, Alpana Saxena and Masroor Mirza contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yadav, P., Mirza, M., Nandi, K. et al. Serum microRNA-21 expression as a prognostic and therapeutic biomarker for breast cancer patients. Tumor Biol. 37, 15275–15282 (2016). https://doi.org/10.1007/s13277-016-5361-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13277-016-5361-y

Keywords

Navigation