Jan YJ, et al. - Given that clinical behavior in prostate cancer (PC) can be predicted by tissue-based gene signatures, researchers wanted to see if this predictive ability could be applied to circulating tumor cells (CTCs) and to demonstrate an association between changes in the signature and changes in clinical behavior. They performed cellular purification and transcriptomic analysis by using an approach that combined the Thermoresponsive(TR)-NanoVelcro CTC purification system with the Nanostring nCounter system. For use in CTCs, they modified the Prostate Cancer Classification System (PCS) panel. Overall 23 PC patients on androgen receptor signaling inhibitors were used to obtain 31 blood samples. The PCS1 Z score (probability) was measured. They succeed in establishing a modified, 16-gene PCS1 signature, which was validated via a meticulous bioinformatics process. This new method affords a way to non-invasively measure contemporary, clinically-relevant gene signatures like PCS in CTCs, as well as enabled measurement of dynamic variations of gene expression in individual patients over time that correlated to ARSI sensitivity. Gene expression can also be related to clinical drug response via these findings.