Circulating microRNAs are associated with docetaxel chemotherapy outcome in castration-resistant prostate cancer

被引：117

作者：

Lin, H-M ^{[1
]}

Castillo, L. ^{[1
]}

Mahon, K. L. ^{[1
,2
]}

Chiam, K. ^{[1
]}

Lee, B. Y. ^{[1
]}

Nguyen, Q. ^{[1
,3
]}

Boyer, M. J. ^{[2
,4
,5
]}

Stockler, M. R. ^{[2
,4
,5
,6
]}

Pavlakis, N. ^{[2
,7
]}

Marx, G. ^{[2
,8
]}

Mallesara, G. ^{[3
,9
]}

Gurney, H. ^{[2
,3
,10
]}

Clark, S. J. ^{[1
,11
]}

Swarbrick, A. ^{[1
,11
]}

Daly, R. J. ^{[12
]}

Horvath, L. G. ^{[1
,2
,3
,4
,5
]}

机构：

[1] St Vincents Hosp, Garvan Inst Med Res, Kinghorn Canc Ctr, Canc Res Div, Darlinghurst, NSW 2010, Australia

[2] Univ Sydney, Sydney Med Sch, Camperdown, NSW 2006, Australia

[3] Pharmacogen Res Individualised Med PRIMe Consorti, Sydney, NSW, Australia

[4] Chris OBrien Lifehouse, Dept Med Oncol, Camperdown, NSW 2050, Australia

[5] Royal Prince Alfred Hosp, Camperdown, NSW 2050, Australia

[6] Concord Repatriat Gen Hosp, Concord, NSW 2139, Australia

[7] Royal N Shore Hosp, St Leonards, NSW 2065, Australia

[8] Sydney Adventist Hosp, Northern Haematol & Oncol Grp, Wahroonga, NSW 2076, Australia

[9] Calvary Mater Newcastle Hosp, Waratah, NSW 2298, Australia

[10] Westmead Hosp, Westmead, NSW 2145, Australia

[11] UNSW Australia, Fac Med, St Vincents Clin Sch, Sydney, NSW, Australia

[12] Monash Univ, Sch Biomed Sci, Signalling Network Lab, Clayton, Vic 3800, Australia

来源：

BRITISH JOURNAL OF CANCER | 2014年 / 110卷 / 10期

基金：

英国医学研究理事会;

关键词：

circulating microRNAs; chemotherapy; metastatic prostate cancer; biomarkers; docetaxel; TUMOR PROGRESSION; MITOXANTRONE; PREDNISONE; EXPRESSION; CELLS; RNA;

D O I：

10.1038/bjc.2014.181

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：2462 / 2471

页数：10

共 37 条

[1] Genomic profiling of MicroRNA and messenger RNA reveals deregulated MicroRNA expression in prostate cancer [J].