An RNA-Based Digital Circulating Tumor Cell Signature Is Predictive of Drug Response and Early Dissemination in Prostate Cancer.

Autor:	Miyamoto DT; Massachusetts General Hospital Cancer Center, Boston, Massachusetts.; Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts., Lee RJ; Massachusetts General Hospital Cancer Center, Boston, Massachusetts.; Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts., Kalinich M; Massachusetts General Hospital Cancer Center, Boston, Massachusetts., LiCausi JA; Massachusetts General Hospital Cancer Center, Boston, Massachusetts., Zheng Y; Massachusetts General Hospital Cancer Center, Boston, Massachusetts., Chen T; Department of Biostatistics & Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts., Milner JD; Massachusetts General Hospital Cancer Center, Boston, Massachusetts., Emmons E; Massachusetts General Hospital Cancer Center, Boston, Massachusetts., Ho U; Massachusetts General Hospital Cancer Center, Boston, Massachusetts., Broderick K; Massachusetts General Hospital Cancer Center, Boston, Massachusetts., Silva E; Massachusetts General Hospital Cancer Center, Boston, Massachusetts., Javaid S; Massachusetts General Hospital Cancer Center, Boston, Massachusetts., Kwan TT; Massachusetts General Hospital Cancer Center, Boston, Massachusetts., Hong X; Massachusetts General Hospital Cancer Center, Boston, Massachusetts., Dahl DM; Massachusetts General Hospital Cancer Center, Boston, Massachusetts.; Department of Urology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts., McGovern FJ; Massachusetts General Hospital Cancer Center, Boston, Massachusetts.; Department of Urology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts., Efstathiou JA; Massachusetts General Hospital Cancer Center, Boston, Massachusetts.; Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts., Smith MR; Massachusetts General Hospital Cancer Center, Boston, Massachusetts.; Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts., Sequist LV; Massachusetts General Hospital Cancer Center, Boston, Massachusetts.; Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts., Kapur R; Massachusetts General Hospital Cancer Center, Boston, Massachusetts., Wu CL; Massachusetts General Hospital Cancer Center, Boston, Massachusetts.; Department of Pathology, Harvard Medical School, Boston, Massachusetts., Stott SL; Massachusetts General Hospital Cancer Center, Boston, Massachusetts.; Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.; Center for Engineering in Medicine, Massachusetts General Hospital, Boston, Massachusetts., Ting DT; Massachusetts General Hospital Cancer Center, Boston, Massachusetts.; Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts., Giobbie-Hurder A; Department of Biostatistics & Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts., Toner M; Center for Engineering in Medicine, Massachusetts General Hospital, Boston, Massachusetts.; Department of Surgery, Harvard Medical School, Boston, Massachusetts., Maheswaran S; Massachusetts General Hospital Cancer Center, Boston, Massachusetts. dhaber@mgh.harvard.edu maheswaran@helix.mgh.harvard.edu.; Department of Surgery, Harvard Medical School, Boston, Massachusetts., Haber DA; Massachusetts General Hospital Cancer Center, Boston, Massachusetts. dhaber@mgh.harvard.edu maheswaran@helix.mgh.harvard.edu.; Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.; Howard Hughes Medical Institute, Chevy Chase, Maryland.
Jazyk:	angličtina
Zdroj:	Cancer discovery [Cancer Discov] 2018 Mar; Vol. 8 (3), pp. 288-303. Date of Electronic Publication: 2018 Jan 04.
DOI:	10.1158/2159-8290.CD-16-1406
Abstrakt:	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 (CTC) using microfluidic cell enrichment followed by digital quantitation of prostate-derived transcripts. In a prospective study of 27 patients with metastatic castration-resistant prostate cancer treated with first-line abiraterone, pretreatment elevation of the digital CTC M 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 of 6 patients with ≤12-month survival, with a subset also expressing the ARV7 splice variant. In a second cohort of 34 men with localized prostate cancer, an elevated preoperative CTC L 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. Significance: There is an unmet need for biomarkers to guide prostate cancer therapies, for curative treatment of localized cancer and for application of molecularly targeted agents in metastatic disease. Digital quantitation of prostate CTC-derived transcripts in blood specimens is predictive of abiraterone response in metastatic cancer and of early dissemination in localized cancer. Cancer Discov; 8(3); 288-303. ©2018 AACR. See related commentary by Heitzer and Speicher, p. 269 This article is highlighted in the In This Issue feature, p. 253 . (©2018 American Association for Cancer Research.)
Databáze:	MEDLINE
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