Phase 2 study of circulating microRNA biomarkers in castration-resistant prostate cancer

Hui-Ming Lin, Kate L. Mahon, Calan Spielman, Howard Gurney, Girish Mallesara, Martin R. Stockler, Patricia Bastick, Karen Briscoe, Gavin Marx, Alexander Swarbrick, Lisa G. Horvath*

*Corresponding author for this work

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Abstract

Background: Biomarkers of therapeutic response and prognosis are needed to assist in the sequencing of treatments for metastatic castration-resistant prostate cancer (CRPC). Previously in a Phase 1 discovery study, we identified 14 circulating microRNAs that were associated with response to docetaxel chemotherapy or overall survival. We performed a Phase 2 validation study to verify these findings. Methods: Using real-Time PCR, the levels of the 14 microRNAs were measured in plasma collected before and after the first cycle of docetaxel from a Phase 2 cohort of 89 patients. Results: The microRNAs were not associated with docetaxel response in the Phase 2 cohort. Higher baseline levels of six microRNAs, predominantly of the miR-200 family, were confirmed to be associated with shorter overall survival. A microRNA signature comprising these six microRNAs predicted high-risk patients in the Phase 2 cohort with a hazard ratio of 4.12 (95% CI 2.20-7.70, P=0.000001). The signature was an independent predictor in multivariable analysis with clinicopathological factors. Conclusions: The association of circulating microRNAs with overall survival suggests their involvement in CRPC progression.

Original languageEnglish
Pages (from-to)1002-1011
Number of pages10
JournalBritish Journal of Cancer
Volume116
Issue number8
Early online date9 Mar 2017
DOIs
Publication statusPublished - 11 Apr 2017
Externally publishedYes

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Keywords

  • circulating microRNA
  • biomarker
  • metastatic prostate cancer

Cite this

Lin, H-M., Mahon, K. L., Spielman, C., Gurney, H., Mallesara, G., Stockler, M. R., ... Horvath, L. G. (2017). Phase 2 study of circulating microRNA biomarkers in castration-resistant prostate cancer. British Journal of Cancer, 116(8), 1002-1011. https://doi.org/10.1038/bjc.2017.50