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

Research output: Contribution to journalArticleResearchpeer-review

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.

LanguageEnglish
Pages1002-1011
Number of pages10
JournalBritish Journal of Cancer
Volume116
Issue number8
Early online date9 Mar 2017
DOIs
Publication statusPublished - 11 Apr 2017
Externally publishedYes

Fingerprint

Castration
MicroRNAs
docetaxel
Prostatic Neoplasms
Biomarkers
Survival
Validation Studies
Real-Time Polymerase Chain Reaction
Drug Therapy
Therapeutics

Bibliographical note

Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

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
Lin, Hui-Ming ; Mahon, Kate L. ; Spielman, Calan ; Gurney, Howard ; Mallesara, Girish ; Stockler, Martin R. ; Bastick, Patricia ; Briscoe, Karen ; Marx, Gavin ; Swarbrick, Alexander ; Horvath, Lisa G. / Phase 2 study of circulating microRNA biomarkers in castration-resistant prostate cancer. In: British Journal of Cancer. 2017 ; Vol. 116, No. 8. pp. 1002-1011.
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Lin, H-M, Mahon, KL, Spielman, C, Gurney, H, Mallesara, G, Stockler, MR, Bastick, P, Briscoe, K, Marx, G, Swarbrick, A & Horvath, LG 2017, 'Phase 2 study of circulating microRNA biomarkers in castration-resistant prostate cancer', British Journal of Cancer, vol. 116, no. 8, pp. 1002-1011. https://doi.org/10.1038/bjc.2017.50

Phase 2 study of circulating microRNA biomarkers in castration-resistant prostate cancer. / Lin, Hui-Ming; Mahon, Kate L.; Spielman, Calan; Gurney, Howard; Mallesara, Girish; Stockler, Martin R.; Bastick, Patricia; Briscoe, Karen; Marx, Gavin; Swarbrick, Alexander; Horvath, Lisa G.

In: British Journal of Cancer, Vol. 116, No. 8, 11.04.2017, p. 1002-1011.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - Phase 2 study of circulating microRNA biomarkers in castration-resistant prostate cancer

AU - Lin, Hui-Ming

AU - Mahon, Kate L.

AU - Spielman, Calan

AU - Gurney, Howard

AU - Mallesara, Girish

AU - Stockler, Martin R.

AU - Bastick, Patricia

AU - Briscoe, Karen

AU - Marx, Gavin

AU - Swarbrick, Alexander

AU - Horvath, Lisa G.

N1 - Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

PY - 2017/4/11

Y1 - 2017/4/11

N2 - 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.

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