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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

97 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2462-2471
Number of pages10
JournalBritish Journal of Cancer
Volume110
Issue number10
DOIs
Publication statusPublished - 13 May 2014
Externally publishedYes

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