An RNA-based digital circulating tumor cell signature is predictive of drug response and early dissemination in prostate cancer
Cancer discovery | 6 Jan 2018
DT Miyamoto, RJ Lee, M Kalinich, J LiCausi, Y Zheng, T Chen, JD Milner, E Emmons, U Ho, K Broderick, E Silva, S Javaid, TT Kwan, X Hong, DM Dahl, FJ McGovern, JA Efstathiou, MR Smith, LV Sequist, R Kapur, CL Wu, SL Stott, DT Ting, A Giobbie-Hurder, M Toner, S Maheswaran and DA Haber
Blood-based biomarkers are critical in metastatic prostate cancer, where characteristic bone metastases are not readily sampled, and they may enable risk stratification in localized disease. We established a sensitive and high-throughput strategy for analyzing prostate circulating tumor cells (CTCs) using microfluidic cell enrichment followed by digital quantitation of prostate-derived transcripts. In a prospective study of 27 metastatic castration-resistant prostate cancer patients treated with first-line abiraterone, pretreatment elevation of the digital CTCM Score identifies a high risk population with poor overall survival (HR 6.0, P=0.01) and short radiographic progression-free survival (HR 3.2, P=0.046). Expression of HOXB13 in CTCs identifies 6/6 patients with ≤12 months survival, with a subset also expressing the AR-V7 splice variant. In a second cohort of 34 men with localized prostate cancer, an elevated preoperative CTCL Score predicts microscopic dissemination to seminal vesicles and/or lymph nodes (P<0.001). Thus, digital quantitation of CTC-specific transcripts enables noninvasive monitoring that may guide treatment selection in both metastatic and localized prostate cancer.
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