4.8 Article

Detection of CTC Clusters and a Dedifferentiated RNA-Expression Survival Signature in Prostate Cancer

Journal

ADVANCED SCIENCE
Volume 6, Issue 2, Pages -

Publisher

WILEY
DOI: 10.1002/advs.201801254

Keywords

circulating tumor cells; GO Chip; microfluidics; prostate cancer; RNA expression

Funding

  1. National Institutes of Health (NIH) Director's New Innovator Award [1DP2OD006672-01]
  2. Department of Defense (DoD) Office of the Congressionally Directed Medical Research Programs (CDMRP) Career Development Award
  3. DOD Physician Research Training Award [W81XWH-14-1-0287]
  4. Prostate Cancer Foundation
  5. A. Alfred Taubman Medical Research Institute
  6. National Science Foundation Graduate Research Fellowship Program [DGE 1256260]

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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.

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