Molecular profiling of prostate cancer with liquid biopsies such as circulating tumor cells (CTC) and cell-free nucleic acid analysis yields informative yet distinct datasets. Additional insights may be gained by simultaneously interrogating multiple liquid biopsy components to construct a more comprehensive molecular disease profile. We conducted an initial proof of principle study aimed at piloting this multi-parametric approach. Peripheral blood samples from men with metastatic castrate resistant prostate cancer (mCRPC) were analyzed simultaneously for CTC enumeration, single cell copy number variation, CTC DNA and matched cell-free DNA mutations, and plasma cell-free RNA levels of androgen receptor (AR) and AR splice variant (AR-V7). In addition, liquid biopsies were compared with matched tumor profiles when available, and a second liquid biopsy was drawn and analyzed at disease progression in a subset of patients. In this manner, multiparametric liquid biopsy profiles were successfully generated for each patient and time point, demonstrating the feasibility of this approach and highlighting shared as well as unique cancer-relevant alterations. With further refinement and validation in large cohorts, multi-parametric liquid biopsies can optimally integrate disparate but clinically informative datasets and maximize their utility for molecularly directed, real-time patient management.
Emmanuelle Hodara, Gareth Morrison, Alexander T. Cunha, Daniel Zainfeld, Tong Xu, Yucheng Xu, Paul W. Dempsey, Paul C. Pagano, Farideh Bischoff, Aditi Khurana, Bonik S. Koo, Marc J. Ting, Philip D. Cotter, Matthew W. Moore, Shelly Gunn, Joshua Usher, Shahrooz Rabizadeh, Peter Danenberg, Kathleen Danenberg, John Carpten, Tanya B. Dorff, David I. Quinn, Amir Goldkorn