Global Gene Expression Characterization of Circulating Tumor Cells in Metastatic Castration-Resistant Prostate Cancer Patients

Background: Current therapeutic options in the course of metastatic castration-resistant prostate cancers (mCRPC) reinforce the need for reliable tools to characterize the tumor in a dynamic way. Circulating tumor cells (CTCs) have emerged as a viable solution to the problem, whereby patients with a variety of solid tumors, including PC, often do not have recent tumor tissue available for analysis. The biomarker characterization in CTCs could provide insights into the current state of the disease and an overall picture of the intra-tumor heterogeneity. Methods: in the present study, we applied a global gene expression characterization of the CTC population from mCRPC (n = 9), with the goal to better understand the biology of these cells and identify the relevant molecules favoring this tumor progression. Results: This analysis allowed the identification of 50 genes specifically expressed in CTCs from patients. Six of these markers (HOXB13, QKI, MAOA, MOSPD1, SDK1, and FGD4), were validated in a cohort of 28 mCRPC, showing clinical interest for the management of these patients. Of note, the activity of this CTC signature was related to the regulation of MYC, a gene strongly implicated in the biology of mCRPC. Conclusions: Overall, our results represent new evidence on the great value of CTCs as a non-invasive biopsy to characterize PC. Briefly, the CTCs were immunoisolated from 7.5 mL of peripheral blood from mCRPC patients (n = 9) at baseline. For that, we used magnetic beads coated with a monoclonal antibody towards the human Epithelial Cell Adhesion Molecule (EpCAM). RNA from isolated CTCs was purified using a kit specifically designed for samples with low cellularity. In parallel, the same protocol was applied to blood samples from healthy donors (n = 6) to establish the baseline of background from unspecific non-CTC immunoisolation. A total RNA extraction, complete Whole Transcriptome Amplification, and gene expression array were performed on samples from the 9 patients and controls.