Phase 2 study of circulating microRNA biomarkers in castration-resistant prostate cancer
BACKGROUND: Biomarkers of therapeutic response and prognosis are needed to assist in the sequencing of treatments for metastatic castration-resistant prostate cancer (CRPC). Previously in a Phase 1 discovery study, we identified 14 circulating microRNAs that were associated with response to docetaxel chemotherapy or overall survival. We performed a Phase 2 validation study to verify these findings. METHODS: Using real-time PCR, the levels of the 14 microRNAs were measured in plasma collected before and after the first cycle of docetaxel from a Phase 2 cohort of 89 patients. RESULTS: The microRNAs were not associated with docetaxel response in the Phase 2 cohort. Higher baseline levels of six microRNAs, predominantly of the miR-200 family, were confirmed to be associated with shorter overall survival. A microRNA signature comprising these six microRNAs predicted high-risk patients in the Phase 2 cohort with a hazard ratio of 4.12 (95% CI 2.20-7.70, P=0.000001). The signature was an independent predictor in multivariable analysis with clinicopathological factors. CONCLUSIONS: The association of circulating microRNAs with overall survival suggests their involvement in CRPC progression.British Journal of Cancer advance online publication 9 March 2017. doi:10.1038/bjc.2017.50 www.bjcancer.com.
|ISBN||1532-1827 (Electronic) 0007-0920 (Linking)|
|Authors||Lin, H. M.; Mahon, K. L.; Spielman, C.; Gurney, H.; Mallesara, G.; Stockler, M. R.; Bastick, P.; Briscoe, K.; Marx, G.; Swarbrick, A.; Horvath, L. G.|
|Responsible Garvan Author|
|Publisher Name||British Journal of Cancer|
|URL link to publisher's version||https://www.ncbi.nlm.nih.gov/pubmed/28278515|
|OpenAccess link to author's accepted manuscript version||https://publications.gimr.garvan.org.au/open-access/14263|