Journal
BRITISH JOURNAL OF CANCER
Volume 110, Issue 10, Pages 2462-2471Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/bjc.2014.181
Keywords
circulating microRNAs; chemotherapy; metastatic prostate cancer; biomarkers; docetaxel
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Funding
- National Health and Medical Research Council of Australia
- Cancer Institute New South Wales
- Cancer Council New South Wales
- Cancer Australia
- Prostate Cancer Foundation of Australia
- Sydney Catalyst
- RT Hall Trust
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Background: Docetaxel is the first-line chemotherapy for castration-resistant prostate cancer (CRPC). However, response rates are similar to 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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