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MicroRNA-10b and minichromosome maintenance complex component 5 gene as prognostic biomarkers in breast cancer

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Tumor Biology

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Abstract

The aim of this study is to identify micro-ribonucleic acid (microRNA) and its target, in addition to their relationship to the outcome in breast cancer (BC). To achieve this aim, we investigated microRNA-10b (miR-10b) and minichromosome maintenance complex component 5 (MCM5 mRNA) expression in 230 breast tissue samples by real-time PCR and semiquantitative conventional RT-PCR, respectively. Relapse-free survival (RFS) associated with miRNA-10b and MCM5 mRNA were tested by Kaplan–Meier survival analysis. The impact of miRNA-10b andMCM5 mRNA expression on the survival was evaluated by Cox proportional hazard regression model. The expression of miRNA-10b and MCM5 mRNA was positive in 86.4 and 79.7 % breast cancer patients, respectively. The overall concordance rate between miRNA-10b and MCM5 RNA was 90.4 %. The median follow-up period was 50 months. The survival analysis showed that high levels of both miR-10b and MCM5 were associated with short relapse free survival of BC. We identified MCM5 mRNA expression changes consistent with the miRNA-10b target regulation. Thus, we could consider miRNA-10b and MCM5 mRNA as prognostic markers and potential therapeutic targets in breast cancer to be applied to other patient data sets.

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Abbreviations

miRNA:

Micro-ribonucleic acids

MCM5 :

Minichromosome maintenance complex component 5

BC:

Breast cancer

BMI:

Body mass index

LN:

Lymph node

ER:

Estrogen receptor

PR:

Progesterone receptor

Her-2 neu:

Human epidermal growth factor receptor 2

IDC:

Invasive duct carcinoma

ILC:

Invasive lobular carcinoma

OCT:

Oral contraceptive therapy

HT:

Hormonal therapy

References

  1. Cava C, Bertoli G, Ripamonti M, Mauri G, Zoppis I, Della Rosa PA, et al. Integration of mRNA expression profile, copy number alterations, and microRNA expression levels in breast cancer to improve grade definition. PLoS One. 2014;9(5):e97681. doi:10.1371/journal.pone.0097681. eCollection 2014.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Liu Z, Zhang XS, Zhang S. Breast tumor subgroups reveal diverse clinical prognostic power. Sci Rep. 2014;4:4002. doi:10.1038/srep04002.

    PubMed  PubMed Central  Google Scholar 

  3. Ma L, Teruya-Feldstein J, Weinberg RA. Tumour invasion and metastasis initiated by microRNA-10b in breast cancer. Nature. 2007;449:682–8. Note: Erratum: Nature 455: 256 only, 2008.

    Article  CAS  PubMed  Google Scholar 

  4. Zhang JJ, Zhao Y, Chait BT, Lathem WW, Ritzi M, Knippers R, Darnell JE. Ser727-dependent recruitment of MCM5 by Stat1alpha in IFN-gamma-induced transcriptional activation. EMBO J. 1998.

  5. Garzon R, Marcucci G, Croce CM. Targeting microRNAs in cancer: rationale, strategies and challenges. Nat Rev Drug Discov. 2010;9(10):775–89. doi:10.1038/nrd3179.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Negrini M, Ferracin M, Sabbioni S, Croce CM. MicroRNAs in humancancer: from research to therapy. J Cell Sci. 2007;120:1833–40.

    Article  CAS  PubMed  Google Scholar 

  7. Ben-Hamo R, Efroni S. MicroRNA-gene association as a prognostic biomarker in cancer exposes disease mechanisms. PLoSComput Biol. 2013;9(11):e1003351. doi:10.1371/journal.pcbi.1003351.

    Google Scholar 

  8. Pinder SE, Elston CW, Ellis IO. Invasive carcinoma: usual histological types. In: Elston CW, Ellis IO, editors. The Breast. 3rd ed. Edinburgh: Churchill Livingstone; 1998. p. 283–337.

    Google Scholar 

  9. Sobin L, Gospodarowicz M, Wittekind C, editors. TNM classification of malignant tumors. 7th ed. Hoboken: John Wiley & Sons, Inc.; 2009.

    Google Scholar 

  10. World Health Organization. International histological classification of tumours. 2nd ed. Geneva: World Health Organization, 1969–1981; Berlin: Springer-Verlag, 1988–Present.

  11. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-delta deltaC(T)) method. Methods. 2001;25:402–8.

    Article  CAS  PubMed  Google Scholar 

  12. Paraskevopoulou MD, Georgakilas G, Kostoulas N, Vlachos IS, Vergoulis T, Reczko M, Filippidis C, Dalamagas T, Hatzigeorgiou AG. DIANA-microT web server v5.0: service integration into miRNA functional analysis workflows. Nucleic Acids Res. 2013 Jul;41(Web Server issue):W169-73. Available at http://diana.cslab.ece.ntua.gr/pathways/ 2013.

  13. Smith SD, Wheeler MA, Plescia J, Colberg JW, Weiss RM, Altieri DC. Urine detection of survivin and diagnosis of breast cancer. JAMA J. 2001;285(3):324–8.

    Article  CAS  Google Scholar 

  14. Meadus WJ. A semi-quantitative RT-PCR method to measure the in vivo effect of dietary conjugated linoleic acid on porcine muscle PPAR gene expression. Biol Proced Online. 2003;5:20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Hayes DF, Isaacs C, Stearns V. Prognostic factors in breast cancer: current and new predictors of metastasis. Journal of Mammary Gland Biology and Neoplasia. 2009;6(4):375–92.

    Article  Google Scholar 

  16. Eo HS, Heo JY, Choi Y, Hwang Y, Choi HS. A pathway-based classification of breast cancer integrating data on differentially expressed genes, copy number variations and microRNA target genes. Molecules and Cells. 2012;34(4):393–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Adam L, Zhong M, Choi W, Qi W, Nicoloso M, Arora A, et al. Clin Cancer Res. 2009;15:5060–72.

    Article  CAS  PubMed  Google Scholar 

  18. Negrini M, Calin GA. Breast cancer metastasis: a microRNA story. Breast Cancer Res. 2008;10:203.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Haque I, Banerjee S, Mehta S, De A, Majumder M, Mayo MS, et al. Cysteine-rich 61-connective tissue growth factor-nephroblastoma-overexpressed 5 (CCN5)/Wnt-1-induced signaling protein-2 (WISP-2) regulates microRNA-10b via hypoxia-inducible factor-1α-TWIST signaling networks in human breast cancer cells. J Biol Chem. 2011;286(50):43475–85. doi:10.1074/jbc.M111.284158.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Ma L, Reinhardt F, Pan E, Soutschek J, Bhat B, Marcusson EG, et al. Therapeutic silencing of miR-10b inhibits metastasis in a mouse mammary tumor model. Nat Biotechnol. 2010;28:341–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Chen W, Cai F, Zhang B, Barekati Z, Zhong XY. The level of circulating miRNA-10b and miRNA-373 in detecting lymph node metastasis of breast cancer: potential biomarkers. Tumour Biol. 2013;34(1):455–62. doi:10.1007/s13277-012-0570-5.

    Article  CAS  PubMed  Google Scholar 

  22. Quinn CM, Wright NA. The clinical assessment of proliferation and growth in human tumours: evaluation of methods and applications as prognostic variables. J Pathol. 1990;160:93–102.

    Article  CAS  PubMed  Google Scholar 

  23. Stoeber K, Tlsty TD, Happerfield L, Thomas GA, Romanov S, Bobrow L, et al. DNA replication licensing and human cell proliferation. J Cell Sci. 2001;114(Pt 11):2027–41.

    CAS  PubMed  Google Scholar 

  24. Freeman A, Morris LS, Mills AD, Stoeber K, Laskey RA, Williams GH, et al. Minichromosome maintenance proteins as biological markers of dysplasia and malignancy. Clin Cancer Res. 1999;5:2121–32.

    CAS  PubMed  Google Scholar 

  25. Del Pino M, Svanholm-Barrie C, Torné A, Marimon L, Gaber J, Sagasta A, et al. mRNA biomarker detection in liquid-based cytology: a new approach in the prevention of cervical cancer. Mod Pathol. 2014. doi:10.1038/modpathol.2014.106.

    Google Scholar 

  26. de Wit M, Kant H, Piersma SR, Pham TV, Mongera S, van Berkel MP, et al. Colorectal cancer candidate biomarkers identified by tissue secretome proteome profiling. J Proteomics. 2014;99:26–39. doi:10.1016/j.jprot.2014.01.001.

    Article  PubMed  Google Scholar 

  27. Place RF, Li LC, Pookot D, Noonan EJ, Dahiya R. MicroRNA-373 induces expression of genes with complementary promoter sequences. Proc Natl Acad Sci U S A. 2008;105(5):1608–13. doi:10.1073/pnas.0707594105.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

This work was supported by Ain Shams University Research Projects 2014-15. Authors are grateful to Professor Fateen Anous, professor of surgery, Ain Shams University, for kindly providing surgical samples and patients data.

Conflicts of interest

None

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Authors and Affiliations

  1. Oncology Diagnostic Unit, Medical Biochemistry and Molecular biology Department, Faculty of Medicine, Ain Shams University, Abbassia, P.O. Box 11381, Cairo, Egypt

    Sanaa Eissa, Marwa Matboli & Hanan H. Shehata

  2. MSc. Pharmacogenetics and Stratified Medicine, University College London, London, UK

    Nada O. E. Essawy

Authors
  1. Sanaa Eissa
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  2. Marwa Matboli
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  3. Hanan H. Shehata
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  4. Nada O. E. Essawy
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Correspondence to Sanaa Eissa.

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Eissa, S., Matboli, M., Shehata, H.H. et al. MicroRNA-10b and minichromosome maintenance complex component 5 gene as prognostic biomarkers in breast cancer. Tumor Biol. 36, 4487–4494 (2015). https://doi.org/10.1007/s13277-015-3090-2

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  • DOI: https://doi.org/10.1007/s13277-015-3090-2

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