Circulating microRNAs are associated with docetaxel chemotherapy outcome in castration-resistant prostate cancer

H. M. Lin, L. Castillo, K. L. Mahon, K. Chiam, B. Y. Lee, Q. Nguyen, M. J. Boyer, M. R. Stockler, N. Pavlakis, G. Marx, G. Mallesara, H. Gurney, S. J. Clark, A. Swarbrick, R. J. Daly, L. G. Horvath

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Background:Docetaxel is the first-line chemotherapy for castration-resistant prostate cancer (CRPC). However, response rates are ∼50% and determined quite late in the treatment schedule, thus non-responders are subjected to unnecessary toxicity. The potential of circulating microRNAs as early biomarkers of docetaxel response in CRPC patients was investigated in this study.Methods:Global microRNA profiling was performed on docetaxel-resistant and sensitive cell lines to identify candidate circulating microRNA biomarkers. Custom Taqman Array MicroRNA cards were used to measure the levels of 46 candidate microRNAs in plasma/serum samples, collected before and after docetaxel treatment, from 97 CRPC patients.Results:Fourteen microRNAs were associated with serum prostate-specific antigen (PSA) response or overall survival, according to Mann-Whitney U or log-rank tests. Non-responders to docetaxel and patients with shorter survival generally had high pre-docetaxel levels of miR-200 family members or decreased/unchanged post-docetaxel levels of miR-17 family members. Multivariate Cox regression with bootstrapping validation showed that pre-docetaxel miR-200b levels, post-docetaxel change in miR-20a levels, pre-docetaxel haemoglobin levels and visceral metastasis were independent predictors of overall survival when modelled together.Conclusions:Our study suggests that circulating microRNAs are potential early predictors of docetaxel chemotherapy outcome, and warrant further investigation in clinical trials.

LanguageEnglish
Pages2462-2471
Number of pages10
JournalBritish Journal of Cancer
Volume110
Issue number10
DOIs
Publication statusPublished - 13 May 2014
Externally publishedYes

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docetaxel
Castration
MicroRNAs
Prostatic Neoplasms
Drug Therapy
Survival
Biomarkers

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Lin, H. M., Castillo, L., Mahon, K. L., Chiam, K., Lee, B. Y., Nguyen, Q., ... Horvath, L. G. (2014). Circulating microRNAs are associated with docetaxel chemotherapy outcome in castration-resistant prostate cancer. British Journal of Cancer, 110(10), 2462-2471. https://doi.org/10.1038/bjc.2014.181
Lin, H. M. ; Castillo, L. ; Mahon, K. L. ; Chiam, K. ; Lee, B. Y. ; Nguyen, Q. ; Boyer, M. J. ; Stockler, M. R. ; Pavlakis, N. ; Marx, G. ; Mallesara, G. ; Gurney, H. ; Clark, S. J. ; Swarbrick, A. ; Daly, R. J. ; Horvath, L. G. / Circulating microRNAs are associated with docetaxel chemotherapy outcome in castration-resistant prostate cancer. In: British Journal of Cancer. 2014 ; Vol. 110, No. 10. pp. 2462-2471.
@article{30bf0f55bb6d43178fbd7f3621e305d5,
title = "Circulating microRNAs are associated with docetaxel chemotherapy outcome in castration-resistant prostate cancer",
abstract = "Background:Docetaxel is the first-line chemotherapy for castration-resistant prostate cancer (CRPC). However, response rates are ∼50{\%} and determined quite late in the treatment schedule, thus non-responders are subjected to unnecessary toxicity. The potential of circulating microRNAs as early biomarkers of docetaxel response in CRPC patients was investigated in this study.Methods:Global microRNA profiling was performed on docetaxel-resistant and sensitive cell lines to identify candidate circulating microRNA biomarkers. Custom Taqman Array MicroRNA cards were used to measure the levels of 46 candidate microRNAs in plasma/serum samples, collected before and after docetaxel treatment, from 97 CRPC patients.Results:Fourteen microRNAs were associated with serum prostate-specific antigen (PSA) response or overall survival, according to Mann-Whitney U or log-rank tests. Non-responders to docetaxel and patients with shorter survival generally had high pre-docetaxel levels of miR-200 family members or decreased/unchanged post-docetaxel levels of miR-17 family members. Multivariate Cox regression with bootstrapping validation showed that pre-docetaxel miR-200b levels, post-docetaxel change in miR-20a levels, pre-docetaxel haemoglobin levels and visceral metastasis were independent predictors of overall survival when modelled together.Conclusions:Our study suggests that circulating microRNAs are potential early predictors of docetaxel chemotherapy outcome, and warrant further investigation in clinical trials.",
author = "Lin, {H. M.} and L. Castillo and Mahon, {K. L.} and K. Chiam and Lee, {B. Y.} and Q. Nguyen and Boyer, {M. J.} and Stockler, {M. R.} and N. Pavlakis and G. Marx and G. Mallesara and H. Gurney and Clark, {S. J.} and A. Swarbrick and Daly, {R. J.} and Horvath, {L. G.}",
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Lin, HM, Castillo, L, Mahon, KL, Chiam, K, Lee, BY, Nguyen, Q, Boyer, MJ, Stockler, MR, Pavlakis, N, Marx, G, Mallesara, G, Gurney, H, Clark, SJ, Swarbrick, A, Daly, RJ & Horvath, LG 2014, 'Circulating microRNAs are associated with docetaxel chemotherapy outcome in castration-resistant prostate cancer', British Journal of Cancer, vol. 110, no. 10, pp. 2462-2471. https://doi.org/10.1038/bjc.2014.181

Circulating microRNAs are associated with docetaxel chemotherapy outcome in castration-resistant prostate cancer. / Lin, H. M.; Castillo, L.; Mahon, K. L.; Chiam, K.; Lee, B. Y.; Nguyen, Q.; Boyer, M. J.; Stockler, M. R.; Pavlakis, N.; Marx, G.; Mallesara, G.; Gurney, H.; Clark, S. J.; Swarbrick, A.; Daly, R. J.; Horvath, L. G.

In: British Journal of Cancer, Vol. 110, No. 10, 13.05.2014, p. 2462-2471.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Circulating microRNAs are associated with docetaxel chemotherapy outcome in castration-resistant prostate cancer

AU - Lin, H. M.

AU - Castillo, L.

AU - Mahon, K. L.

AU - Chiam, K.

AU - Lee, B. Y.

AU - Nguyen, Q.

AU - Boyer, M. J.

AU - Stockler, M. R.

AU - Pavlakis, N.

AU - Marx, G.

AU - Mallesara, G.

AU - Gurney, H.

AU - Clark, S. J.

AU - Swarbrick, A.

AU - Daly, R. J.

AU - Horvath, L. G.

PY - 2014/5/13

Y1 - 2014/5/13

N2 - Background:Docetaxel is the first-line chemotherapy for castration-resistant prostate cancer (CRPC). However, response rates are ∼50% and determined quite late in the treatment schedule, thus non-responders are subjected to unnecessary toxicity. The potential of circulating microRNAs as early biomarkers of docetaxel response in CRPC patients was investigated in this study.Methods:Global microRNA profiling was performed on docetaxel-resistant and sensitive cell lines to identify candidate circulating microRNA biomarkers. Custom Taqman Array MicroRNA cards were used to measure the levels of 46 candidate microRNAs in plasma/serum samples, collected before and after docetaxel treatment, from 97 CRPC patients.Results:Fourteen microRNAs were associated with serum prostate-specific antigen (PSA) response or overall survival, according to Mann-Whitney U or log-rank tests. Non-responders to docetaxel and patients with shorter survival generally had high pre-docetaxel levels of miR-200 family members or decreased/unchanged post-docetaxel levels of miR-17 family members. Multivariate Cox regression with bootstrapping validation showed that pre-docetaxel miR-200b levels, post-docetaxel change in miR-20a levels, pre-docetaxel haemoglobin levels and visceral metastasis were independent predictors of overall survival when modelled together.Conclusions:Our study suggests that circulating microRNAs are potential early predictors of docetaxel chemotherapy outcome, and warrant further investigation in clinical trials.

AB - Background:Docetaxel is the first-line chemotherapy for castration-resistant prostate cancer (CRPC). However, response rates are ∼50% and determined quite late in the treatment schedule, thus non-responders are subjected to unnecessary toxicity. The potential of circulating microRNAs as early biomarkers of docetaxel response in CRPC patients was investigated in this study.Methods:Global microRNA profiling was performed on docetaxel-resistant and sensitive cell lines to identify candidate circulating microRNA biomarkers. Custom Taqman Array MicroRNA cards were used to measure the levels of 46 candidate microRNAs in plasma/serum samples, collected before and after docetaxel treatment, from 97 CRPC patients.Results:Fourteen microRNAs were associated with serum prostate-specific antigen (PSA) response or overall survival, according to Mann-Whitney U or log-rank tests. Non-responders to docetaxel and patients with shorter survival generally had high pre-docetaxel levels of miR-200 family members or decreased/unchanged post-docetaxel levels of miR-17 family members. Multivariate Cox regression with bootstrapping validation showed that pre-docetaxel miR-200b levels, post-docetaxel change in miR-20a levels, pre-docetaxel haemoglobin levels and visceral metastasis were independent predictors of overall survival when modelled together.Conclusions:Our study suggests that circulating microRNAs are potential early predictors of docetaxel chemotherapy outcome, and warrant further investigation in clinical trials.

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DO - 10.1038/bjc.2014.181

M3 - Article

VL - 110

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EP - 2471

JO - British Journal of Cancer

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JF - British Journal of Cancer

SN - 0007-0920

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