Skip to main content

Advertisement

SpringerLink
Log in

Dysregulated miR1254 and miR579 for cardiotoxicity in patients treated with bevacizumab in colorectal cancer

  • Research Article
  • Published:
Tumor Biology

Abstract

Methods for detecting circulating microRNAs (miRNAs), small RNAs that control gene expression, at high sensitivity and specificity in the blood have been reported in recent studies. The goal of this study was to determine if detectable levels of specific miRNAs are released into the circulation for bevacizumab-induced cardiotoxicity. A miRNA array analysis was performed using RNA isolated from 10 control patients in bevacizumab treatment, and n = 10 patients have been confirmed to have bevacizumab-induced cardiotoxicity. From the array, we selected 19 candidate miRNA for a second validation study in 90 controls and 88 patients with bevacizumab-induced cardiotoxicity. Consistent with the data obtained from the microRNA array, circulating levels of five miRNAs were significantly increased in patients with bevacizumab-induced cardiotoxicity compared with controls. To confirm these data, we compared selected miRNAs in the plasma of patients with bevacizumab-induced cardiotoxicity with those of 66 patients with acute myocardial infarction (AMI). Moreover, we went on to analyze what factors may influence the levels of potential biomarker miRNAs. Consistent with the data obtained from the microRNA array, circulating levels of five miRNAs were significantly increased in patients with bevacizumab-induced cardiotoxicity compared with those of healthy bevacizumab treatment controls. However, only miRNA1254 and miRNA579 showed high specificity in the validation experiments. Moreover, we went on to analyze what factors may influence the levels of potential biomarker miRNAs. We identify two miRNAs that are specifically elevated in patients with bevacizumab-induced cardiotoxicity, miR1254 and miRNA579, and miRNA1254 shows the strongest correlation to the clinical diagnosis of bevacizumab-induced cardiotoxicity.

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. Miles DW, Dieras V, Cortes J, Duenne AA, Yi J, O'Shaughnessy J. First-line bevacizumab in combination with chemotherapy for HER2-negative metastatic breast cancer: pooled and subgroup analyses of data from 2447 patients. Ann Oncol. 2013;24:2773–80.

    Article  CAS  PubMed  Google Scholar 

  2. Kruzliak P, Novak J, Novak M. Vascular endothelial growth factor inhibitor-induced hypertension: from pathophysiology to prevention and treatment based on long-acting nitric oxide donors. Am J Hypertens. 2013.

  3. Choueiri TK, Mayer EL, Je Y, et al. Congestive heart failure risk in patients with breast cancer treated with bevacizumab. J Clin Oncol. 2011;29:632–8.

    Article  CAS  PubMed  Google Scholar 

  4. Trimarchi S, Tsai T, Eagle KA, et al. Acute abdominal aortic dissection: insight from the International Registry of Acute Aortic Dissection (IRAD). J Vasc Surg. 2007;46:913–9.

    Article  PubMed  Google Scholar 

  5. Nesi G, Anichini C, Tozzini S, Boddi V, Calamai G, Gori F. Pathology of the thoracic aorta: a morphologic review of 338 surgical specimens over a 7-year period. Cardiovasc Pathol. 2009;18:134–9.

    Article  PubMed  Google Scholar 

  6. Bossone E, Pyeritz RE, O'Gara P, et al. Acute aortic dissection in blacks: insights from the International Registry of Acute Aortic Dissection. Am J Med. 2013;126:909–15.

    Article  PubMed  Google Scholar 

  7. Spittell PC, Spittell Jr JA, Joyce JW, et al. Clinical features and differential diagnosis of aortic dissection: experience with 236 cases (1980 through 1990). Mayo Clin Proc. 1993;68:642–51.

    Article  CAS  PubMed  Google Scholar 

  8. Razzouk L, Fusaro M, Esquitin R. Novel biomarkers for risk stratification and identification of life-threatening cardiovascular disease: troponin and beyond. Curr Cardiol Rev. 2012;8:109–15.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  9. Ranasinghe AM, Bonser RS. Biomarkers in acute aortic dissection and other aortic syndromes. J Am Coll Cardiol. 2010;56:1535–41.

    Article  CAS  PubMed  Google Scholar 

  10. van Rooij E, Olson EN. MicroRNAs: powerful new regulators of heart disease and provocative therapeutic targets. J Clin Invest. 2007;117:2369–76.

    Article  PubMed Central  PubMed  Google Scholar 

  11. Scalbert E, Bril A. Implication of microRNAs in the cardiovascular system. Curr Opin Pharmacol. 2008;8:181–8.

    Article  CAS  PubMed  Google Scholar 

  12. Care A, Catalucci D, Felicetti F, et al. MicroRNA-133 controls cardiac hypertrophy. Nat Med. 2007;13:613–8.

    Article  CAS  PubMed  Google Scholar 

  13. Schroen B, Heymans S. MicroRNAs and beyond: the heart reveals its treasures. Hypertension. 2009;54:1189–94.

    Article  CAS  PubMed  Google Scholar 

  14. Thum T, Galuppo P, Wolf C, et al. MicroRNAs in the human heart: a clue to fetal gene reprogramming in heart failure. Circulation. 2007;116:258–67.

    Article  CAS  PubMed  Google Scholar 

  15. van Rooij E, Sutherland LB, Liu N, et al. A signature pattern of stress-responsive microRNAs that can evoke cardiac hypertrophy and heart failure. Proc Natl Acad Sci U S A. 2006;103:18255–60.

    Article  PubMed Central  PubMed  Google Scholar 

  16. Mitchell PS, Parkin RK, Kroh EM, et al. Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci. 2008;105:10513–8.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  17. Ai J, Zhang R, Li Y, et al. Circulating microRNA-1 as a potential novel biomarker for acute myocardial infarction. Biochem Biophys Res Commun. 2010;391:73–7.

    Article  CAS  PubMed  Google Scholar 

  18. Ji X, Takahashi R, Hiura Y, Hirokawa G, Fukushima Y, Iwai N. Plasma miR-208 as a biomarker of myocardial injury. Clin Chem. 2009;55:1944–9.

    Article  CAS  PubMed  Google Scholar 

  19. Suzuki T, Katoh H, Watanabe M, et al. Novel biochemical diagnostic method for aortic dissection. Results of a prospective study using an immunoassay of smooth muscle myosin heavy chain. Circulation. 1996;93:1244–9.

    Article  CAS  PubMed  Google Scholar 

  20. Berezikov E, Thuemmler F, van Laake LW, et al. Diversity of microRNAs in human and chimpanzee brain. Nat Genet. 2006;38:1375–7.

    Article  CAS  PubMed  Google Scholar 

  21. Ruijter JM, Ramakers C, Hoogaars WM, et al. Amplification efficiency: linking baseline and bias in the analysis of quantitative PCR data. Nucleic Acids Res. 2009;37:e45.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  22. Amacher DE, Schomaker SJ, Aubrecht J. Development of blood biomarkers for drug-induced liver injury: an evaluation of their potential for risk assessment and diagnostics. Mol Diagn Ther. 2013;17:343–54.

    Article  CAS  PubMed  Google Scholar 

  23. 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 

  24. Ng EK, Chong WW, Jin H, et al. Differential expression of microRNAs in plasma of patients with colorectal cancer: a potential marker for colorectal cancer screening. Gut. 2009;58:1375–81.

    Article  CAS  PubMed  Google Scholar 

  25. Brase JC, Johannes M, Schlomm T, et al. Circulating miRNAs are correlated with tumor progression in prostate cancer. Int J Cancer. 2011;128:608–16.

    Article  CAS  PubMed  Google Scholar 

  26. Patz Jr EF, Campa MJ, Gottlin EB, Kusmartseva I, Guan XR, Herndon 2nd JE. Panel of serum biomarkers for the diagnosis of lung cancer. J Clin Oncol. 2007;25:5578–83.

    Article  PubMed  Google Scholar 

  27. Foss KM, Sima C, Ugolini D, Neri M, Allen KE, Weiss GJ. miR-1254 and miR-574–5p: serum-based microRNA biomarkers for early-stage non-small cell lung cancer. J Thorac Oncol. 2011;6:482–8.

    Article  PubMed  Google Scholar 

  28. Wiesen JL, Tomasi TB. Dicer is regulated by cellular stresses and interferons. Mol Immunol. 2009;46:1222–8.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We thank Ms. Min Ding and Dr. Melissa Cruz of the Institute of Shanghai and Springer Media for the critical review of the manuscript. This work was supported by the Foundation of Tianjin Health Bureau Technology (grant number 11KG143) and AfterTumor Technology (Aftertumor.com) with grant number 11305CN.

Conflicts of interest

The authors declare that they have no competing interests.

Author information

Authors and Affiliations

  1. Department of Vascular Surgery, Tianhe Hospital, Tianjing, 300050, People’s Republic of China

    Ziyuan Zhao, Ju He, Jing Zhang, Meng Liu, Sin Yang, Nan Li & Xiaofeng Li

Authors
  1. Ziyuan Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ju He
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jing Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Meng Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Sin Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Nan Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Xiaofeng Li
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ziyuan Zhao.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zhao, Z., He, J., Zhang, J. et al. Dysregulated miR1254 and miR579 for cardiotoxicity in patients treated with bevacizumab in colorectal cancer. Tumor Biol. 35, 5227–5235 (2014). https://doi.org/10.1007/s13277-014-1679-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13277-014-1679-5

Keywords

Search

Navigation