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- Title
Circulating microRNAs are associated with docetaxel chemotherapy outcome in castration-resistant prostate cancer.
- Authors
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
- 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.
- Subjects
MICRORNA; DOCETAXEL; CANCER chemotherapy; HEALTH outcome assessment; CASTRATION; DRUG resistance in cancer cells; PROSTATE cancer treatment
- Publication
British Journal of Cancer, 2014, Vol 110, Issue 10, p2462
- ISSN
0007-0920
- Publication type
Article
- DOI
10.1038/bjc.2014.181