Skip to main content

Serum miR-30c Level Predicted Cardiotoxicity in Non-small Cell Lung Cancer Patients Treated with Bevacizumab

Cardiovascular Toxicology volume 18, pages 284–289 (2018)Cite this article

Abstract

Cardiotoxicity is a common adverse effect induced by drug chemotherapy. miR-30c has been reported to be involved in the progress of heart diseases. In the present study, miR-30c was used to predict the cardiotoxicity in non-small cell lung cancer (NSCLC) patients treated with bevacizumab chemotherapy. Eighty NSCLC patients were included in this study. Serum miR-30c levels were detected at pre-chemotherapy, during-chemotherapy (the 2nd, 4th, and 8th week) and 1 month after chemotherapy. miR-30c expression was elevated with the duration of the chemotherapy cycle and decreased 1 month after chemotherapy. The correlation analysis showed that serum miR-30c levels were positively related to cardiotoxicity before chemotherapy and during chemotherapy. ROC curve analysis showed the values of AUC, sensitivity, and specificity for the level of miR-30c alteration (from pre-chemotherapy to during-chemotherapy) were 0.851, 0.720, and 0.860, respectively. Serum miR-30c level is elevated during bevacizumab chemotherapy, which is probably an early detection biomarker for predicting cardiotoxicity in NSCLC patients treated with drug chemotherapy.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

43,34 €

Price includes VAT (Finland)
Tax calculation will be finalised during checkout.

Fig. 1
Fig. 2
Fig. 3

References

  1. Siegel, R., et al. (2014). Cancer statistics, 2014. CA: A Cancer Journal for Clinicians, 64(1), 9–29.

    Google Scholar 

  2. Iyer, S., et al. (2014). The symptom burden of non-small cell lung cancer in the USA: A real-world cross-sectional study. Supportive Care in Cancer, 22(1), 181–187.

    Article  PubMed  Google Scholar 

  3. Gridelli, C., et al. (2007). The role of bevacizumab in the treatment of non-small cell lung cancer: Current indications and future developments. The Oncologist, 12(10), 1183–1193.

    Article  PubMed  CAS  Google Scholar 

  4. Lauro, S., et al. (2014). The use of bevacizumab in non-small cell lung cancer: An update. Anticancer Research, 34(4), 1537–1545.

    PubMed  CAS  Google Scholar 

  5. Ding, L., et al. (2014). The efficacy and safety of pemetrexed plus bevacizumab in previously treated patients with advanced non-squamous non-small cell lung cancer (ns-NSCLC). Tumor Biology, 36(4), 2491–2499.

    Google Scholar 

  6. Kruzliak, P., Novak, J., & Novak, M. (2014). Vascular endothelial growth factor inhibitor-induced hypertension: From pathophysiology to prevention and treatment based on long-acting nitric oxide donors. American Journal of Hypertension, 27(1), 3–13.

    Article  PubMed  CAS  Google Scholar 

  7. Choueiri, T. K., et al. (2011). Congestive heart failure risk in patients with breast cancer treated with bevacizumab. Journal of Clinical Oncology, 29(6), 632–638.

    Article  PubMed  CAS  Google Scholar 

  8. Yeung, S. L., Lam, H. S., & Schooling, C. M. (2017). Vascular endothelial growth factor and ischemic heart disease risk: A mendelian randomization study. Journal of the American Heart Association, 6(8), e005619.

    Article  Google Scholar 

  9. Hueso, L., et al. (2017). Dynamics and implications of circulating anti-angiogenic VEGF-A165b isoform in patients with ST-elevation myocardial infarction. Scientific Reports, 7(1), 9962.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Wang, X., et al. (2017). Intratracheal administration of isosorbide dinitrate improves pulmonary artery pressure and ventricular remodeling in a rat model of heart failure following myocardial infarction. Experimental and Therapeutic Medicine, 14(2), 1399–1408.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Sandhu, H., & Maddock, H. (2014). Molecular basis of cancer-therapy-induced cardiotoxicity: Introducing microRNA biomarkers for early assessment of subclinical myocardial injury. Clinical Science, 126(6), 377–400.

    Article  PubMed  CAS  Google Scholar 

  12. Bartel, D. P. (2004). MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell, 116(2), 281–297.

    Article  PubMed  CAS  Google Scholar 

  13. Lawrence, P., & Ceccoli, J. (2017). Advances in the application and impact of MicroRNAs as therapies for skin disease. BioDrugs, 31(5), 423–438.

    Article  CAS  Google Scholar 

  14. Pallez, D., Gardes, J., & Pasquier, C. (2017). Prediction of miRNA-disease associations using an evolutionary tuned latent semantic analysis. Scientific Reports, 7(1), 10548.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  15. Hirt, M. N., et al. (2015). Deciphering the microRNA signature of pathological cardiac hypertrophy by engineered heart tissue- and sequencing-technology. Journal of Molecular and Cellular Cardiology, 81, 1–9.

    Article  PubMed  CAS  Google Scholar 

  16. Hou, Y., et al. (2012). Beta-adrenoceptor regulates miRNA expression in rat heart. Medical Science Monitor, 18(8), BR309–BR314.

    Google Scholar 

  17. Bao, J. L., & Lin, L. (2014). MiR-155 and miR-148a reduce cardiac injury by inhibiting NF-kappaB pathway during acute viral myocarditis. European Review for Medical and Pharmacological Sciences, 18(16), 2349–2356.

    PubMed  Google Scholar 

  18. Lagos-Quintana, M., et al. (2002). Identification of tissue-specific microRNAs from mouse. Current Biology, 12(9), 735–739.

    Article  PubMed  CAS  Google Scholar 

  19. Abonnenc, M., et al. (2013). Extracellular matrix secretion by cardiac fibroblasts: Role of microRNA-29b and microRNA-30c. Circulation Research, 113(10), 1138–1147.

    Article  PubMed  CAS  Google Scholar 

  20. Yanaihara, N., et al. (2006). Unique microRNA molecular profiles in lung cancer diagnosis and prognosis. Cancer Cell, 9(3), 189–198.

    Article  PubMed  CAS  Google Scholar 

  21. Panizo, S., et al. (2017) Regulation of miR-29b and miR-30c by vitamin D receptor activators contributes to attenuate uraemia-induced cardiac fibrosis. Nephrology Dialysis Transplantation, 32(11), 1831–1840

    Article  Google Scholar 

  22. Martín, M., et al. (2009). Minimizing cardiotoxicity while optimizing treatment efficacy with trastuzumab: Review and expert recommendations. The Oncologist, 14(1), 1–11.

    Article  PubMed  CAS  Google Scholar 

  23. Cakmak, H., et al. (2017). Effects of sunitinib and bevacizumab on VEGF and miRNA levels on corneal neovascularization. Cutaneous and Ocular Toxicology, 37(2), 191–195.

    Google Scholar 

  24. Ferrara, N., Hillan, K. J. & Novotny, W. (2005). Bevacizumab (Avastin), a humanized anti-VEGF monoclonal antibody for cancer therapy. Biochemical and Biophysical Research Communications, 333(2), 328–335.

    Article  PubMed  CAS  Google Scholar 

  25. Giordano, F. J., et al. (2001). A cardiac myocyte vascular endothelial growth factor paracrine pathway is required to maintain cardiac function. Proceedings of the National Academy of Sciences of the United States of America, 98(10), 5780–5785.

  26. Hong, I. H., & Park, S. P. (2017). Quantitative physiological measurements to evaluate the response of antivascular endothelial growth factor treatment in patients with neovascular diseases. Indian Journal of Ophthalmology, 65(7), 559–568.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Deuse, T., et al. (2009). Hepatocyte growth factor or vascular endothelial growth factor gene transfer maximizes mesenchymal stem cell-based myocardial salvage after acute myocardial infarction. Circulation, 120(11 Suppl), S247–S254.

    Google Scholar 

  28. Liu, X., et al. (2016). miR-30c regulates proliferation, apoptosis and differentiation via the Shh signaling pathway in P19 cells. Experimental & Molecular Medicine, 48(7), e248.

    Article  CAS  Google Scholar 

  29. Gu, Y., et al. (2013). miR-30b and miR-30c expression predicted response to tyrosine kinase inhibitors as first line treatment in non-small cell lung cancer. Chinese Medical Journal, 126(23), 4435–4439.

    PubMed  CAS  Google Scholar 

  30. Jentzsch, C., et al. (2012). A phenotypic screen to identify hypertrophy-modulating microRNAs in primary cardiomyocytes. Journal of Molecular and Cellular Cardiology, 52(1), 13–20.

    Article  PubMed  CAS  Google Scholar 

  31. Irani, S., & Hussain, M. M. (2015). Role of microRNA-30c in lipid metabolism, adipogenesis, cardiac remodeling and cancer. Current Opinion in Lipidology, 26(2), 139–146.

    Article  PubMed  CAS  Google Scholar 

  32. Sayed, D., et al. (2007). MicroRNAs play an essential role in the development of cardiac hypertrophy. Circulation Research, 100(3), 416–424.

    Article  PubMed  CAS  Google Scholar 

  33. Duisters, R.F., et al. (2009). miR-133 and miR-30 regulate connective tissue growth factor: Implications for a role of microRNAs in myocardial matrix remodeling. Circulation Research, 104(2), 170–178.

    Article  PubMed  CAS  Google Scholar 

  34. Chino, H., et al. (2016). Cardiogenic syncope possibly related to bevacizumab-containing combination chemotherapy for advanced non-small cell lung cancer. Journal of Thoracic Disease, 8(9), 2646–2650.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Affiliations

  1. Department of Thoracic Surgery, TianJin Chest Hospital, 261 Taierzhuang South Rd., Tianjin, 300222, People’s Republic of China

    Fang Zhou, Xike Lu & Xun Zhang

Authors
  1. Fang Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xike Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xun Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Xike Lu.

Ethics declarations

Conflict of interest

The authors declare no conflict of interest.

Additional information

Handling Editor: Gen Suzuki

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOC 101 KB)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Zhou, F., Lu, X. & Zhang, X. Serum miR-30c Level Predicted Cardiotoxicity in Non-small Cell Lung Cancer Patients Treated with Bevacizumab. Cardiovasc Toxicol 18, 284–289 (2018). https://doi.org/10.1007/s12012-018-9457-z

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12012-018-9457-z

Keywords

  • miR-30c
  • Cardiotoxicity
  • Lung cancer
  • Human