An RNA-Based Digital Circulating Tumor Cell Signature Is Predictive of Drug Response and Early Dissemination in Prostate Cancer
Abstract
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 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 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 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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Mar 01, 2018
- Source ID
- 10.1158/2159-8290.cd-16-1406
Entities
People
- Anita Giobbie-hurder
- Chin-lee Wu
- Daniel Haber
- David T Ting
- David T. Miyamoto
- Douglas M. Dahl
- Erin Emmons
- Erin Silva
- Francis J. Mcgovern
- Hong Xin
- Jason A. Efstathiou
- John D. Milner
- Joseph A. Licausi
- Katherine Broderick
- Lecia V. Sequist
- Mark Kalinich
- Matthew R Smith
- Mehmet Toner
- Ravi Kapur
- Richard J. Lee
- Sarah Javaid
- Shannon L. Stott
- Shyamala Maheswaran
- Tanya Todorova Kwan
- Tianqi Chen
- Uyen Ho
- Yu Zheng
Organizations
- Burroughs Wellcome Fund
- Dana–Farber Cancer Institute
- Harvard Medical School
- Howard Hughes Medical Institute
- Massachusetts General Hospital
- National Institute of Biomedical Imaging and Bioengineering
- National Institute of General Medical Sciences
- Prostate Cancer Foundation
- United States Department of Defense