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Down-regulation of miRNA-30a in human plasma is a novel marker for breast cancer

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Abstract

The present study was to evaluate the value of miRNA-30a in plasma as potential tumor marker in detecting breast cancer (BC). Using a novel approach to extract miRNA-30a from the plasma followed by real-time quantitative polymerase chain reaction (RQ-PCR) analysis, levels of miRNA-30a were quantified in plasma specimens of 100 BCs and 64 age-matched and disease-free healthy controls (HC). And we compared the diagnostic value of plasma miRNA-30a with conventional circulating tumor markers CA153 and CEA. The median levels of miRNA-30a were significantly lower in preoperative BC than those in HC (P < 0.001). The levels of CEA and CA153 were all significantly higher in preoperative BC compared with those in HC (P = 0.008 and P = 0.001, respectively), and only the level of CA153 decreased in postoperative BC compared with preoperative BC (P = 0.015). ROC analysis showed the sensitivity and specificity of miRNA-30a for BC diagnosis at 74.0 and 65.6 %, respectively, whereas the sensitivities of CEA and CA153 were 12.0 and 14.0 %, respectively. The status of ER and triple-negative BC was significantly associated with miRNA-30a level (P = 0.007 and P = 0.005, respectively). And no other clinicopathological features were found to had significant difference. Our findings suggest that plasma miRNA-30a decreased in patients with BC and has great potential to use as novel biomarkers for BC diagnosis.

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Abbreviations

HC:

Healthy controls

CEA:

Carcinoembryonic antigen

CA153:

Carbohydrate antigen 153

TNM:

Tumor-node-metastasis

AJCC:

American Joint Committee on Cancer

ROC:

Receiver operator characteristic

ER:

Estrogen receptor

LNM:

Lymph node metastasis

BC:

Breast cancer

RQ-PCR:

Real-time quantitative polymerase chain reaction

DCIS:

Ductal carcinoma in situ

References

  1. 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.

    Article  PubMed  Google Scholar 

  2. Screening for breast cancer. U.S. preventive services task force recommendation statement. Ann Intern Med. 2009;151(10):716–26. W-236.

    Google Scholar 

  3. Mandelblatt JS, Cronin KA, Bailey S, Berry DA, de Koning HJ, Draisma G, et al. Effects of mammography screening under different screening schedules: model estimates of potential benefits and harms. Ann Intern Med. 2009;151(10):738–47.

    PubMed  Google Scholar 

  4. O’Hanlon DM, Kerin MJ, Kent P, Maher D, Grimes H, Given HF. An evaluation of preoperative CA 15–3 measurement in primary breast carcinoma. Br J Cancer. 1995;71(6):1288–91.

    Article  PubMed  Google Scholar 

  5. Uehara M, Kinoshita T, Hojo T, Akashi-Tanaka S, Iwamoto E, Fukutomi T. Long-term prognostic study of carcinoembryonic antigen (CEA) and carbohydrate antigen 15–3 (CA 15–3) in breast cancer. Int J Clin Oncol. 2008;13(5):447–51.

    Article  PubMed  CAS  Google Scholar 

  6. Mettlin C, Littrup PJ, Kane RA, Murphy GP, Lee F, Chesley A, et al. Relative sensitivity and specificity of serum prostate specific antigen (PSA) level compared with age-referenced PSA, PSA density, and PSA change. Data from the American cancer society national prostate cancer detection project. Cancer. 1994;74(5):1615–20.

    Article  PubMed  CAS  Google Scholar 

  7. Jiang J, Lee EJ, Gusev Y, Schmittgen TD. Real-time expression profiling of microRNA precursors in human cancer cell lines. Nucleic Acids Res. 2005;33(17):5394–403.

    Article  PubMed  CAS  Google Scholar 

  8. 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.

    Article  PubMed  CAS  Google Scholar 

  9. Johnson R, Zuccato C, Belyaev ND, Guest DJ, Cattaneo E, Buckley NJ. A microRNA-based gene dysregulation pathway in Huntington’s disease. Neurobiol Dis. 2008;29(3):438–45.

    Article  PubMed  CAS  Google Scholar 

  10. 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(15):2128–36.

    Article  PubMed  CAS  Google Scholar 

  11. Calin GA, Dumitru CD, Shimizu M, Bichi R, Zupo S, Noch E, et al. Frequent deletions and down-regulation of micro- RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proc Natl Acad Sci USA. 2002;99(24):15524–9.

    Article  PubMed  CAS  Google Scholar 

  12. Huang Z, Huang D, Ni S, Peng Z, Sheng W, Du X. Plasma microRNAs are promising novel biomarkers for early detection of colorectal cancer. Int J Cancer. 2010;127(1):118–26.

    Article  PubMed  CAS  Google Scholar 

  13. 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 USA. 2008;105(30):10513–8.

    Article  PubMed  CAS  Google Scholar 

  14. Xu J, Wu C, Che X, Wang L, Yu D, Zhang T, et al. Circulating microRNAs, miR-21, miR-122, and miR-223, in patients with hepatocellular carcinoma or chronic hepatitis. Mol Carcinog. 2011;50(2):136–42.

    Article  PubMed  CAS  Google Scholar 

  15. Yaman Agaoglu F, 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. Tumour Biol. 2011;32(3):583–8.

    Article  PubMed  CAS  Google Scholar 

  16. Lawrie CH, Gal S, Dunlop HM, Pushkaran B, Liggins AP, Pulford K, et al. Detection of elevated levels of tumour-associated microRNAs in serum of patients with diffuse large B-cell lymphoma. Br J Haematol. 2008;141(5):672–5.

    Article  PubMed  Google Scholar 

  17. Resnick KE, Alder H, Hagan JP, Richardson DL, Croce CM, Cohn DE. The detection of differentially expressed microRNAs from the serum of ovarian cancer patients using a novel real-time PCR platform. Gynecol Oncol. 2009;112(1):55–9.

    Article  PubMed  CAS  Google Scholar 

  18. Zhu W, Qin W, Atasoy U, Sauter ER. Circulating microRNAs in breast cancer and healthy subjects. BMC Res Notes. 2009;2:89.

    Article  PubMed  Google Scholar 

  19. Porika M, Malotu N, Veldandi UK, Yadala N, Abbagani S. Evaluation of tumor markers in southern Indian breast cancer patients. Asian Pac J Cancer Prev. 2010;11(1):157–9.

    PubMed  Google Scholar 

  20. Guo LJ, Zhang QY. Decreased serum miR-181a is a potential new tool for breast cancer screening. Int J Mol Med. 2012;30(3):680–6.

    PubMed  CAS  Google Scholar 

  21. Molina R, Auge JM, Farrus B, Zanon G, Pahisa J, Munoz M, et al. Prospective evaluation of carcinoembryonic antigen (CEA) and carbohydrate antigen 15.3 (CA 15.3) in patients with primary locoregional breast cancer. Clin Chem. 2009;56(7):1148–57.

    Article  Google Scholar 

  22. Shu J, Li CG, Liu YC, Yan XC, Xu X, Huang XE, et al. Comparison of serum tumor associated material (TAM) with conventional biomarkers in cancer patients. Asian Pac J Cancer Prev. 2012;13(5):2399–403.

    Article  PubMed  Google Scholar 

  23. Carey LA, Perou CM, Livasy CA, Dressler LG, Cowan D, Conway K, et al. Race, breast cancer subtypes, and survival in the Carolina. Breast Cancer Res Treat. 2012;134(3):1081–93.

    Article  Google Scholar 

  24. Dent R, Trudeau M, Pritchard KI, Hanna WM, Kahn HK, Sawka CA, et al. Triple-negative breast cancer: clinical features and patterns of recurrence. Clin Cancer Res. 2007;13(15 Pt 1):4429–34.

    Article  PubMed  Google Scholar 

  25. Smid M, Wang Y, Zhang Y, Sieuwerts AM, Yu J, Klijn JG, et al. Subtypes of breast cancer show preferential site of relapse. Cancer Res. 2008;68(9):3108–14.

    Article  PubMed  CAS  Google Scholar 

  26. Cheng CW, Wang HW, Chang CW, Chu HW, Chen CY, Yu JC, et al. MicroRNA-30a inhibits cell migration and invasion by downregulating vimentin expression and is a potential prognostic marker in breast cancer. Breast Cancer Res Treat. 2012;134(3):1081–93.

    Article  PubMed  CAS  Google Scholar 

  27. Rodriguez-Gonzalez FG, Sieuwerts AM, Smid M, Look MP, Meijer-van Gelder ME, de Weerd V, et al. MicroRNA-30c expression level is an independent predictor of clinical benefit of endocrine therapy in advanced estrogen receptor positive breast cancer. Breast Cancer Res Treat. 2011;127(1):43–51.

    Article  PubMed  CAS  Google Scholar 

  28. Heinzelmann J, Henning B, Sanjmyatav J, Posorski N, Steiner T, Wunderlich H, et al. Specific miRNA signatures are associated with metastasis and poor prognosis in clear cell renal cell carcinoma. World J Urol. 2011;29(3):367–73.

    Article  PubMed  CAS  Google Scholar 

  29. Tan X, Qin W, Zhang L, Hang J, Li B, Zhang C, et al. A 5-microRNA signature for lung squamous cell carcinoma diagnosis and hsa-miR-31 for prognosis. Clin Cancer Res. 2011;17(21):6802–11.

    Article  PubMed  CAS  Google Scholar 

  30. Yu Y, Yang L, Zhao M, Zhu S, Kang R, Vernon P, et al. Targeting microRNA-30a-mediated autophagy enhances imatinib activity against human chronic myeloid leukemia cells. Leukemia. 2012;26(8):1752–60.

    Article  PubMed  CAS  Google Scholar 

  31. Noviello C, Courjal F, Theillet C. Loss of heterozygosity on the long arm of chromosome 6 in breast cancer: possibly four regions of deletion. Clin Cancer Res. 1996;2(9):1601–6.

    PubMed  CAS  Google Scholar 

  32. Chappell SA, Walsh T, Walker RA, Shaw JA. Loss of heterozygosity at chromosome 6q in preinvasive and early invasive breast carcinomas. Br J Cancer. 1997;75(9):1324–9.

    Article  PubMed  CAS  Google Scholar 

  33. dos Santos LG, Lopes-Costa PV, dos Santos AR, Facina G, da Silva BB. Bcl-2 oncogene expression in estrogen receptor-positive and negative breast carcinoma. Eur J Gynaecol Oncol. 2008;29(5):459–61.

    PubMed  Google Scholar 

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Acknowledgments

This work was supported by Wenzhou Science and Technology Bureau (Grant numbers Y20100008, Y20080081) and Health Bureau of Zhejiang Province (Grant number 2009B106).

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Correspondence to Guan-li Huang.

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Zeng, Rc., Zhang, W., Yan, Xq. et al. Down-regulation of miRNA-30a in human plasma is a novel marker for breast cancer. Med Oncol 30, 477 (2013). https://doi.org/10.1007/s12032-013-0477-z

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