Circulating microRNAs are associated with docetaxel chemotherapy outcome in castration-resistant prostate cancer.
Circulating microRNAs are associated with docetaxel chemotherapy outcome in castration-resistant prostate cancer.
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DOI：
10.1038/bjc.2014.181
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发表时间：
2014-05-13
影响因子：
8.8
通讯作者：
Horvath, L. G.
中科院分区：
文献类型：
--
作者：
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.
多西他赛是去势抵抗性前列腺癌（CRPC）的一线化疗药物。然而，响应率为50%左右，并且在治疗方案中相当晚才确定，因此无响应者会受到不必要的毒性。本研究探讨了循环microRNA作为CRPC患者多西他赛应答早期生物标志物的潜力。对紫杉醇耐药和敏感细胞系进行总体microRNA分析，以鉴定候选循环microRNA生物标志物。使用定制Taqman Array MicroRNA卡测量来自97名CRPC患者的多西他赛治疗前后收集的血浆/血清样品中46种候选microRNA的水平。根据Mann-Whitney U或对数秩检验，14种microRNA与血清前列腺特异性抗原（PSA）反应或总生存期相关。多西他赛无应答者和生存期较短的患者通常多西他赛治疗前miR-200家族成员水平较高，或多西他赛治疗后miR-17家族成员水平降低/不变。多变量考克斯回归和自举验证显示，多西他赛治疗前miR-200 b水平、多西他赛治疗后miR-20 a水平变化、多西他赛治疗前血红蛋白水平和内脏转移是总生存期的独立预测因素。我们的研究表明，循环microRNA是多西他赛化疗结果的潜在早期预测因子，值得在临床试验中进一步研究。
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. 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. 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. 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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影响因子：
3.7
作者：
Mercatelli N;Coppola V;Bonci D;Miele F;Costantini A;Guadagnoli M;Bonanno E;Muto G;Frajese GV;De Maria R;Spagnoli LG;Farace MG;Ciafrè SA
通讯作者：
Ciafrè SA
影响因子：
5.7
作者：
Kutanzi, Kristy R.;Yurchenko, Olga V.;Beland, Frederick A.;Checkhun, Vasyl' F.;Pogribny, Igor P.
通讯作者：
Pogribny, Igor P.
影响因子：
3.2
作者：
Gonzales, Jason C.;Fink, Louis M.;Ward, David C.
通讯作者：
Ward, David C.
影响因子：
6.4
作者：
Brase, Jan C.;Johannes, Marc;Sueltmann, Holger
通讯作者：
Sueltmann, Holger
影响因子：
8.8
作者：
Bryant, R. J.;Pawlowski, T.;Catto, J. W. F.;Marsden, G.;Vessella, R. L.;Rhees, B.;Kuslich, C.;Visakorpi, T.;Hamdy, F. C.
通讯作者：
Hamdy, F. C.