Cell type specific gene expression analysis of prostate needle biopsies resolves tumor tissue heterogeneity

Oncotarget. 2015 Jan 20;6(2):1302-14. doi: 10.18632/oncotarget.2744.

Abstract

A lack of cell surface markers for the specific identification, isolation and subsequent analysis of living prostate tumor cells hampers progress in the field. Specific characterization of tumor cells and their microenvironment in a multi-parameter molecular assay could significantly improve prognostic accuracy for the heterogeneous prostate tumor tissue. Novel functionalized gold-nano particles allow fluorescence-based detection of absolute mRNA expression levels in living cells by fluorescent activated flow cytometry (FACS). We use of this technique to separate prostate tumor and benign cells in human prostate needle biopsies based on the expression levels of the tumor marker alpha-methylacyl-CoA racemase (AMACR). We combined RNA and protein detection of living cells by FACS to gate for epithelial cell adhesion molecule (EPCAM) positive tumor and benign cells, EPCAM/CD45 double negative mesenchymal cells and CD45 positive infiltrating lymphocytes. EPCAM positive epithelial cells were further sub-gated into AMACR high and low expressing cells. Two hundred cells from each population and several biopsies from the same patient were analyzed using a multiplexed gene expression profile to generate a cell type resolved profile of the specimen. This technique provides the basis for the clinical evaluation of cell type resolved gene expression profiles as pre-therapeutic prognostic markers for prostate cancer.

MeSH terms

  • Antigens, Neoplasm / genetics
  • Antigens, Neoplasm / metabolism
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Biopsy, Needle
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / metabolism
  • Epithelial Cell Adhesion Molecule
  • Flow Cytometry
  • Gene Expression Profiling / methods*
  • Gene Expression Regulation, Neoplastic*
  • Genetic Heterogeneity
  • Humans
  • Leukocyte Common Antigens / genetics
  • Leukocyte Common Antigens / metabolism
  • Male
  • Prognosis
  • Prostate / metabolism*
  • Prostate / pathology
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology
  • Racemases and Epimerases / genetics
  • Racemases and Epimerases / metabolism
  • Reproducibility of Results
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tumor Cells, Cultured

Substances

  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • Cell Adhesion Molecules
  • Epithelial Cell Adhesion Molecule
  • Leukocyte Common Antigens
  • Racemases and Epimerases
  • alpha-methylacyl-CoA racemase