Detection of CTC clusters and a dedifferentiated RNA-expression survival signature in prostate cancer

M Kozminsky, S Fouladdel, J Chung, Y Wang, DC Smith, A Alva, E Azizi, T Morgan, S Nagrath. “Detection of CTC clusters and a dedifferentiated RNA‐expression survival signature in prostate cancer.” Advanced Science 6.2 (2019): 1801254.

Abstract: Rates of progression and treatment response in advanced prostate cancer are highly variable, necessitating non-invasive methods to assess the molecular characteristics of these tumors in real time. The unique potential of circulating tumor cells (CTCs) to serve as a clinically useful liquid biomarker is due to their ability to inform via both enumeration and RNA expression. A microfluidic graphene oxide-based device (GO Chip) is used to isolate CTCs and CTC clusters from the whole blood of 41 men with metastatic castration-resistant prostate cancer. Additionally, the expression of 96 genes of interest is determined by RT-qPCR. Multivariate analyses are conducted to determine the genes most closely associated with overall survival, PSA progression, and radioclinical progression. A preliminary signature, comprising high expression of stemness genes and low expression of epithelial and mesenchymal genes, potentially implicates an undifferentiated CTC phenotype as a marker of poor prognosis in this setting.