TY - JOUR
T1 - Circulating microRNAs are associated with docetaxel chemotherapy outcome in castration-resistant prostate cancer
AU - Lin, Hui-Ming
AU - Castillo, Lesley
AU - Mahon, Kate
AU - Chiam, Karen
AU - Lee, Brian
AU - Nguyen, Quoc
AU - Boyer, Michael
AU - Stockler, Martin
AU - Pavlakis, Nick
AU - MARX, Gavin
AU - Mallesara, Girish
AU - Gurney, Howard
AU - Clark, Susan
AU - Swarbrick, Alexander
AU - Daly, Roger
AU - Horvath, Lisa
PY - 2014
Y1 - 2014
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.
UR - http://www.scopus.com/inward/record.url?scp=84900548218&partnerID=8YFLogxK
U2 - 10.1038/bjc.2014.181
DO - 10.1038/bjc.2014.181
M3 - Article
SN - 0007-0920
VL - 110
SP - 2462
EP - 2471
JO - British Journal of Cancer
JF - British Journal of Cancer
IS - 10
ER -
