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Combination of miR-21 with Circulating Tumor Cells Markers Improve Diagnostic Specificity of Metastatic Breast Cancer

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Abstract

Circulating miR-21 is upregulated in breast cancer. However, correlation of miR-21 expression with clinic pathologic characteristics remains questionable. In this study, we investigate whether combination of circulation miR-21 with circulating tumor cells (CTCs) marker (EpCAM, MUS1, HER2) could improve diagnostic specificity of metastatic breast cancer. Total 223 breast cancer patients were included. 89 % patients were associated with upregulation of miR-21 compared with health control. 20 % patients were detected for CTCs marker positive. For higher specificity purpose, triple marker positive samples were selected as true CTCs positive, which only occupied 59.5 % of total metastatic breast cancer patients. Specificity of detection of CTCs was 96.7 %. Furthermore, 59.5 % metastatic breast cancer patients were shown both abnormal miR-21 and true CTCs positive according to distribution of true CTCs positive and abnormal miR-21; Combination of miR-21 and CTCs was increased specificity of metastatic detection to 100 %. Our findings suggested that combination of miR-21 with CTCs marker could be used for better diagnosis of metastatic breast cancer in the future.

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References

  1. DeSantis, C. E., Lin, C. C., Mariotto, A. B., et al. (2014). Cancer treatment and survivorship statistics, 2014. CA: A Cancer Journal for Clinicians, 64(4), 252–271.

    Google Scholar 

  2. Cristofanilli, M., Ellis, M. J., Budd, G. T., et al. (2004). Circulating tumor cells, disease progression, and survival in metastatic breast cancer. New England Journal of Medicine, 351, 781–791.

    Article  CAS  PubMed  Google Scholar 

  3. Cristofanilli, M., Hayes, D. F., Budd, G. T., et al. (2005). Circulating tumor cells: a novel prognostic factor for newly diagnosed metastatic breast cancer. Journal of Clinical Oncology, 23, 1420–1430.

    Article  PubMed  Google Scholar 

  4. Borgen, E., Wiedswang, G., Karesen, R., et al. (2004). Isolatedtumor cells in bone marrow three years after diagnosis in disease-free breast cancer patients predict unfavorable clinicaloutcome. Clinical Cancer Research, 10, 5342–5348.

    Article  PubMed  Google Scholar 

  5. Gilbey, A. M., Burnett, D., Coleman, R. E., & Holen, I. (2004). The detection of circulating breast cancer cells in blood. Journal of Clinical Pathology, 57, 903–911.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  6. Okumura, Y., Jotsuka, T., Nakano, S., et al. (2004). Persistent evidence of circulating tumor cells detected by means of RT-PCR for CEAmRNA predicts early relapse: a prospective study in node-negative breast cancer. Surgery, 135, 419–426.

    Article  PubMed  Google Scholar 

  7. Kwon, S., Kang, S. H., Ro, J., Jeon, C. H., Park, J. W., & Lee, E. S. (2005). The melanoma antigen gene as a surveillance marker for the detection of circulating tumor cells in patients with breast carcinoma. Cancer, 104, 251–256.

    Article  CAS  PubMed  Google Scholar 

  8. Miyashiro, I., Huynh, K., Kuo, C., et al. (2001). Molecular strategy for detecting metastatic cancers with use of multiple tumor-specific MAGE-A genes. Clinical Chemistry, 47, 505–512.

    CAS  PubMed  Google Scholar 

  9. Reinholz, M. M., Nibbe, A., Jonart, L. M., et al. (2005). Evaluation of a panel of tumor markers for molecular detection of circulating cancer cells in women with suspected breast cancer. Clinical Cancer Research, 11, 3722–3732.

    Article  CAS  PubMed  Google Scholar 

  10. Ring, A. E., Zabaglo, L., Ormerod, M. G., Smith, I. E., & Dowsett, M. (2005). Detection of circulating epithelial cells in the blood of patients with breast cancer: comparison of three techniques. British Journal of Cancer, 92, 906–912.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  11. Sabbatini, R., Morselli, M., Federico, M., et al. (2000). Detection of circulating tumor cells by reverse transcriptase polymerase chain reaction of maspin in patients with breast cancer undergoing conventional-dose chemotherapy. Journal of Clinical Oncology, 18, 1914–1920.

    CAS  PubMed  Google Scholar 

  12. Taback, B., Chan, A. D., Kuo, C. T., et al. (2001). Detection of occult metastatic breast cancer cells in blood by a multimolecular marker assay: Correlation with clinical stage of disease. Cancer Research, 61, 8845–8850.

    CAS  PubMed  Google Scholar 

  13. Weigelt, B., Bosma, A. J., Hart, A. A., Rodenhuis, S., & van’t Veer, L. J. (2003). Marker genes for circulating tumour cells predict survival in metastasized breast cancer patients. British Journal of Cancer, 88, 1091–1094.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  14. Hayes, D. F., Budd, G. T., Cristofanilli, M., et al. (2006). Circulating tumor cells at each follow-up time point during therapy of metastatic breast cancer patients predict progression-free and overall survival. Clinical Cancer Research, 12, 4218–4224.

    Article  CAS  PubMed  Google Scholar 

  15. Zabaglo, L., Ormerod, M. G., Parton, M., Ring, A., Smith, I. E., & Dowsett, M. (2003). Cell filtration-laser scanning cytometry for the characterisation of circulating breast cancer cells. Cytometry A, 55, 102–108.

    Article  PubMed  Google Scholar 

  16. Zehentner, B. K., Secrist, H., Hayes, D. C., et al. (2006). Detection of circulating tumor cells in peripheral blood of breast cancer patients during or after therapy using a multigene real-time RT-PCR assay. Molecular Diagnosis and Therapy, 10, 41–47.

    Article  CAS  PubMed  Google Scholar 

  17. Zhang, B., Pan, X., Cobb, G. P., et al. (2007). MicroRNAs as oncogenes and tumor suppressors. Development Biology, 302, 1–12.

    Article  CAS  Google Scholar 

  18. Zheng, D. L., Haddadin, S., Wang, Y., et al. (2011). Plasma microRNAs as novel biomarkers for early detection of lung cancer. International Journal of Clinical and Experimental Pathology, 4, 575–586.

    PubMed Central  CAS  PubMed  Google Scholar 

  19. Li, T., Leong, M. H., Harms, B., et al. (2013). MicroRNA-21 as a potential colon and rectal cancer biomarker. World Journal of Gastroenterology, 19(34), 5615–5621.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  20. Yang, X. R., Du Gao, Y. N., et al. (2013). Serum microRNA-21 as a diagnostic marker for lung carcinoma: A systematic review and meta analysis. Plos One, 9(5), e97460.

    Article  Google Scholar 

  21. Zeng, Z. Y., Wang, J. G., Zhao, L. Y., et al. (2013). Potential role of microRNA-21 in the diagnosis of gastric cancer: a meta-analysis. Plos One, 8(9), e73278.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  22. Kroh, E. M., Parkin, R. K., Mitchell, P. S., & Tewari, M. (2010). Analysis of circulating microRNA biomarkers in plasma and serum using quantitative reverse transcription-PCR (qRT-PCR). Methods, 50(4), 298–301.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  23. Phua, Y. L., & Ho, J. (2014). MicroRNAs in the pathogenesis of cystic kidney disease. Current Opinion in Pediatrics [Epub ahead of print].

  24. Alečković, M., & Kang, Y. (2014). Regulation of cancer metastasis by cell-free miRNAs. Biochimica et Biophysica Acta, 1855(1), 24–42.

    PubMed  Google Scholar 

  25. Gallach, S., Calabuig-Fariñas, S., Jantus-Lewintre, E., & Camps, C. (2014). MicroRNAs:promising new antiangiogenic targets in cancer. BioMed Research International, 2014, 878450.

    Article  PubMed Central  PubMed  Google Scholar 

  26. Suzuki, H. I., Katsura, A., Matsuyama, H., & Miyazono, K. (2014). MicroRNA regulons in tumor microenvironment. Oncogene. doi:10.1038/onc.2014.254.

  27. Croset, M., Santini, D., Iuliani, M., Fioramonti, M., Zoccoli, A., Vincenzi, B., et al. (2014). MicroRNAs and bone metastasis: a new challenge. Molecules, 19(7), 10115–10128.

    Article  PubMed  Google Scholar 

  28. Sekar, D., Hairul Islam, V. I., Thirugnanasambantham, K., & Saravanan, S. (2014). Relevance of miR-21 in HIV and non-HIV-related lymphomas. Tumor Biology, 35(9), 8387–8393.

    Article  CAS  PubMed  Google Scholar 

  29. Kang, C., Song, J. J., Lee, J., & Kim, M. Y. (2014). Epigenetics: An emerging player in gastric cancer. World Journal Gastroenterol., 20(21), 6433–6447.

    Article  Google Scholar 

  30. Iorio, M. V., Ferracin, M., Liu, C. G., Veronese, A., Spizzo, R., Sabbioni, S., et al. (2005). MicroRNA gene expression deregulation in human breast cancer. Cancer Research, 65(16), 7065–7070.

    Article  CAS  PubMed  Google Scholar 

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    Authors and Affiliations

    1. Departments of Surgery, People’s Hospital of Linzi District, Affiliated to Binzhou Medical College, Zibo, 255400, China

      Xingwang Yang & Xiaoming Wang

    2. Department of Thyroid and Breast Surgery, Linyi People’s Hospital, Linyi, 276003, Shandong, China

      Hongyan Shen & Kecheng Xue

    3. Lunan Pharmaceutical Group Co., Ltd., Linyi, 276005, Shandong, China

      Rong Deng

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    1. Xingwang Yang
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    2. Xiaoming Wang
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    3. Hongyan Shen
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    4. Rong Deng
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    5. Kecheng Xue
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    Correspondence to Kecheng Xue.

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    Xingwang Yang and Xiaoming Wang have contributed equally to this work.

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    Yang, X., Wang, X., Shen, H. et al. Combination of miR-21 with Circulating Tumor Cells Markers Improve Diagnostic Specificity of Metastatic Breast Cancer. Cell Biochem Biophys 73, 87–91 (2015). https://doi.org/10.1007/s12013-015-0573-0

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