Skip to main content

Advertisement

SpringerLink
Log in

The level of circulating miRNA-10b and miRNA-373 in detecting lymph node metastasis of breast cancer: potential biomarkers

  • Research Article
  • Published:
Tumor Biology

Abstract

MicroRNAs (miRNAs) are a class of small noncoding RNAs whose expression changes are associated with cancer development and invasion. We hypothesized that miR-10b and miR-373, which are increased in lymphatic metastatic tissues, could be directly assayed in the plasma and used to detect the lymph node status of breast cancer patients. Between November 2009 and January 2012, 35 breast ductal carcinoma patients with lymph node metastasis (N patients), 25 ductal carcinoma patients without lymph node metastasis (N0 patients), and ten healthy female donors were enrolled in the study. Circulating miR-10b and miR-373 were determined in preoperative plasma samples by reverse transcription quantitative real-time PCR assay. In preliminary tests, the plasma levels of circulating miR-10b and miR-373 were found to be significantly higher in ten breast cancer patients with lymph node metastasis compared to ten N0 patients and ten normal donors (P < 0.01). On validation analysis, the median value level of miR-10b in the 35 N patients was 4.44-fold (P < 0.01) increased, and miR-373 was 4.38-fold (P < 0.01) increased in comparison to the 25 N0 patients. MiR-10b was used for differentiation of N patients from N0 patients; the odds ratio was 2.19, and the value of the area under the receiver-operating curve (AUC) was 0.80, with sensitivity of 71 % and specificity of 72 %. For miR-373, the odds ratio was 2.62, and the AUC was 0.84, with sensitivity of 68 % and specificity of 89 %. A combination of the two circulating miRNAs further enhanced the sensitivity to 72 % and the specificity to 94.3 %. Our data suggest that circulating miRNA-10b and miRNA-373 are potential biomarkers for detecting the lymph node status of breast cancer.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Heneghan HM, Miller N, Lowery AJ, Sweeney KJ, Kerin MJ. MicroRNAs as novel biomarkers for breast cancer. J Oncol. 2009;2009:950201. doi:10.1155/2010/950201.

    PubMed  CAS  Google Scholar 

  2. Darby S, McGale P, Correa C, Taylor C, Arriagada R, Clarke M, et al. Effect of radiotherapy after breast-conserving surgery on 10-year recurrence and 15-year breast cancer death: meta-analysis of individual patient data for 10,801 women in 17 randomised trials. Lancet. 2011;378(9804):1707–16. doi:10.1016/S0140-6736(11)61629-2.

    Article  PubMed  CAS  Google Scholar 

  3. Wiatrek R, Kruper L. Sentinel lymph node biopsy indications and controversies in breast cancer. Maturitas. 2011;69(1):7–10. doi:10.1016/j.maturitas.2011.02.006.

    Article  PubMed  Google Scholar 

  4. Boyd NF, Guo H, Martin LJ, Sun L, Stone J, Fishell E, et al. Mammographic density and the risk and detection of breast cancer. N Engl J Med. 2007;356(3):227–36. doi:10.1056/NEJMoa062790.

    Article  PubMed  CAS  Google Scholar 

  5. Taplin S, Abraham L, Barlow WE, Fenton JJ, Berns EA, Carney PA, et al. Mammography facility characteristics associated with interpretive accuracy of screening mammography. J Natl Cancer Inst. 2008;100(12):876–87. doi:10.1093/jnci/djn172.

    Article  PubMed  Google Scholar 

  6. Baek D, Villen J, Shin C, Camargo FD, Gygi SP, Bartel DP. The impact of microRNAs on protein output. Nature. 2008;455(7209):64–71. doi:10.1038/nature07242.

    Article  PubMed  CAS  Google Scholar 

  7. Munker R, Calin GA. MicroRNA profiling in cancer. Clin Sci (Lond). 2011;121(4):141–58. doi:10.1042/CS20110005.

    Article  CAS  Google Scholar 

  8. 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(7):673–82. doi:10.1634/theoncologist.2010-0103.

    Article  PubMed  Google Scholar 

  9. Valastyan S, Reinhardt F, Benaich N, Calogrias D, Szasz AM, Wang ZC, et al. A pleiotropically acting microRNA, miR-31, inhibits breast cancer metastasis. Cell. 2009;137(6):1032–46. doi:10.1016/j.cell.2009.03.047.

    Article  PubMed  CAS  Google Scholar 

  10. Kong W, Yang H, He L, Zhao JJ, Coppola D, Dalton WS, et al. MicroRNA-155 is regulated by the transforming growth factor beta/Smad pathway and contributes to epithelial cell plasticity by targeting RhoA. Mol Cell Biol. 2008;28(22):6773–84. doi:10.1128/MCB.00941-08.

    Article  PubMed  CAS  Google Scholar 

  11. Tavazoie SF, Alarcon C, Oskarsson T, Padua D, Wang Q, Bos PD, et al. Endogenous human microRNAs that suppress breast cancer metastasis. Nature. 2008;451(7175):147–52. doi:10.1038/nature06487.

    Article  PubMed  CAS  Google Scholar 

  12. Huang Q, Gumireddy K, Schrier M, le Sage C, Nagel R, Nair S, et al. The microRNAs miR-373 and miR-520c promote tumour invasion and metastasis. Nat Cell Biol. 2008;10(2):202–10. doi:10.1038/ncb1681.

    Article  PubMed  CAS  Google Scholar 

  13. Ma L, Teruya-Feldstein J, Weinberg RA. Tumour invasion and metastasis initiated by microRNA-10b in breast cancer. Nature. 2007;449(7163):682–8. doi:10.1038/nature06174.

    Article  PubMed  CAS  Google Scholar 

  14. 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(16):7065–70. doi:10.1158/0008-5472.CAN-05-1783.

    Article  PubMed  CAS  Google Scholar 

  15. Wei J, Gao W, Zhu CJ, Liu YQ, Mei Z, Cheng T, et al. Identification of plasma microRNA-21 as a biomarker for early detection and chemosensitivity of non-small cell lung cancer. Chin J Cancer. 2011;30(6):407–14.

    Article  PubMed  CAS  Google Scholar 

  16. Komatsu S, Ichikawa D, Takeshita H, Tsujiura M, Morimura R, Nagata H, et al. Circulating microRNAs in plasma of patients with oesophageal squamous cell carcinoma. Br J Cancer. 2011;105(1):104–11. doi:10.1038/bjc.2011.198.

    Article  PubMed  CAS  Google Scholar 

  17. Akobeng AK. Understanding diagnostic tests 3: receiver operating characteristic curves. Acta Paediatr. 2007;96(5):644–7. doi:10.1111/j.1651-2227.2006.00178.x.

    Article  PubMed  Google Scholar 

  18. Gonzalez-Angulo AM, Morales-Vasquez F, Hortobagyi GN. Overview of resistance to systemic therapy in patients with breast cancer. Adv Exp Med Biol. 2007;608:1–22.

    Article  PubMed  CAS  Google Scholar 

  19. Petronella P, Scorzelli M, Benevento R, Corbisiero MC, Freda F, Canonico S. The sentinel lymph node: a suitable technique in breast cancer treatment? Ann Ital Chir. 2012;83(2):119–23.

    PubMed  Google Scholar 

  20. Weir HK, Thun MJ, Hankey BF, Ries LA, Howe HL, Wingo PA, et al. Annual report to the nation on the status of cancer, 1975–2000, featuring the uses of surveillance data for cancer prevention and control. J Natl Cancer Inst. 2003;95(17):1276–99.

    Article  PubMed  Google Scholar 

  21. Yen TW, Hunt KK, Ross MI, Mirza NQ, Babiera GV, Meric-Bernstam F, et al. Predictors of invasive breast cancer in patients with an initial diagnosis of ductal carcinoma in situ: a guide to selective use of sentinel lymph node biopsy in management of ductal carcinoma in situ. J Am Coll Surg. 2005;200(4):516–26. doi:10.1016/j.jamcollsurg.2004.11.012.

    Article  PubMed  Google Scholar 

  22. Son BK, Bong JG, Park SH, Jeong YJ. Ductal carcinoma in situ and sentinel lymph node biopsy. J Breast Cancer. 2011;14(4):301–7. doi:10.4048/jbc.2011.14.4.301.

    Article  PubMed  Google Scholar 

  23. Zhao FL, Hu GD, Wang XF, Zhang XH, Zhang YK, Yu ZS. Serum overexpression of microRNA-10b in patients with bone metastatic primary breast cancer. J Int Med Res. 2012;40(3):859–66.

    PubMed  CAS  Google Scholar 

  24. Roth C, Rack B, Muller V, Janni W, Pantel K, Schwarzenbach H. Circulating microRNAs as blood-based markers for patients with primary and metastatic breast cancer. Breast Cancer Res. 2010;12(6):R90. doi:10.1186/bcr2766.

    Article  PubMed  CAS  Google Scholar 

  25. Fu SW, Chen L, Man YG. miRNA biomarkers in breast cancer detection and management. J Cancer. 2011;2:116–22.

    Article  PubMed  CAS  Google Scholar 

  26. Li Z, Gu X, Fang Y, Xiang J, Chen Z. MicroRNA expression profiles in human colorectal cancers with brain metastases. Oncol Lett. 2012;3(2):346–50. doi:10.3892/ol.2011.497ol-03-02-0346.

    PubMed  CAS  Google Scholar 

  27. Li QJ, Zhou L, Yang F, Wang GX, Zheng H, Wang DS et al. MicroRNA-10b promotes migration and invasion through CADM1 in human hepatocellular carcinoma cells. Tumour Biol. 2012. doi:10.1007/s13277-012-0396-1.

  28. Wu X, Weng L, Li X, Guo C, Pal SK, Jin JM, et al. Identification of a 4-microRNA signature for clear cell renal cell carcinoma metastasis and prognosis. PLoS One. 2012;7(5):e35661. doi:10.1371/journal.pone.0035661PONE-D-11-19678.

    Article  PubMed  CAS  Google Scholar 

  29. Wang L, Alcon A, Yuan H, Ho J, Li QJ, Martins-Green M. Cellular and molecular mechanisms of pomegranate juice-induced anti-metastatic effect on prostate cancer cells. Integr Biol (Camb). 2011;3(7):742–54. doi:10.1039/c0ib00122h.

    Article  CAS  Google Scholar 

  30. Zhao H, Shen J, Medico L, Wang D, Ambrosone CB, Liu S. A pilot study of circulating miRNAs as potential biomarkers of early stage breast cancer. PLoS One. 2010;5(10):e13735. doi:10.1371/journal.pone.0013735.

    Article  PubMed  Google Scholar 

  31. Valadi H, Ekstrom K, Bossios A, Sjostrand M, Lee JJ, Lotvall JO. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol. 2007;9(6):654–9. doi:10.1038/ncb1596.

    Article  PubMed  CAS  Google Scholar 

  32. Turchinovich A, Weiz L, Langheinz A, Burwinkel B. Characterization of extracellular circulating microRNA. Nucleic Acids Res. 2011;39(16):7223–33. doi:10.1093/nar/gkr254.

    Article  PubMed  CAS  Google Scholar 

  33. Hanke M, Hoefig K, Merz H, Feller AC, Kausch I, Jocham D, et al. A robust methodology to study urine microRNA as tumor marker: microRNA-126 and microRNA-182 are related to urinary bladder cancer. Urol Oncol. 2010;28(6):655–61. doi:10.1016/j.urolonc.2009.01.027.

    Article  PubMed  CAS  Google Scholar 

  34. Park NJ, Zhou H, Elashoff D, Henson BS, Kastratovic DA, Abemayor E, et al. Salivary microRNA: discovery, characterization, and clinical utility for oral cancer detection. Clin Cancer Res. 2009;15(17):5473–7. doi:1078-0432.CCR-09-0736.

    Article  PubMed  CAS  Google Scholar 

  35. Zubakov D, Boersma AW, Choi Y, van Kuijk PF, Wiemer EA, Kayser M. MicroRNA markers for forensic body fluid identification obtained from microarray screening and quantitative RT-PCR confirmation. Int J Legal Med. 2010;124(3):217–26. doi:10.1007/s00414-009-0402-3.

    Article  PubMed  Google Scholar 

  36. Yuan A, Farber EL, Rapoport AL, Tejada D, Deniskin R, Akhmedov NB, et al. Transfer of microRNAs by embryonic stem cell microvesicles. PLoS One. 2009;4(3):e4722. doi:10.1371/journal.pone.0004722.

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by the Swiss National Science Foundation (320030-124958/1).

Conflicts of interest

None.

Author information

Authors and Affiliations

  1. Laboratory for Gynecological Oncology, University Women’s Hospital, Department of Biomedicine, University of Basel, Hebelstrasse 20, CH4031, Basel, Switzerland

    Weijie Chen, Fengfeng Cai, Bei Zhang, Zeinab Barekati & Xiao Yan Zhong

Authors
  1. Weijie Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Fengfeng Cai
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Bei Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Zeinab Barekati
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Xiao Yan Zhong
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Xiao Yan Zhong.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Chen, W., Cai, F., Zhang, B. et al. The level of circulating miRNA-10b and miRNA-373 in detecting lymph node metastasis of breast cancer: potential biomarkers. Tumor Biol. 34, 455–462 (2013). https://doi.org/10.1007/s13277-012-0570-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13277-012-0570-5

Keywords

Search

Navigation