A basal stem cell signature identifies aggressive prostate cancer phenotypes

BA Smith, A Sokolov, V Uzunangelov… - Proceedings of the …, 2015 - National Acad Sciences
BA Smith, A Sokolov, V Uzunangelov, R Baertsch, Y Newton, K Graim, C Mathis, D Cheng…
Proceedings of the National Academy of Sciences, 2015National Acad Sciences
Evidence from numerous cancers suggests that increased aggressiveness is accompanied
by up-regulation of signaling pathways and acquisition of properties common to stem cells. It
is unclear if different subtypes of late-stage cancer vary in stemness properties and whether
or not these subtypes are transcriptionally similar to normal tissue stem cells. We report a
gene signature specific for human prostate basal cells that is differentially enriched in
various phenotypes of late-stage metastatic prostate cancer. We FACS-purified and …
Evidence from numerous cancers suggests that increased aggressiveness is accompanied by up-regulation of signaling pathways and acquisition of properties common to stem cells. It is unclear if different subtypes of late-stage cancer vary in stemness properties and whether or not these subtypes are transcriptionally similar to normal tissue stem cells. We report a gene signature specific for human prostate basal cells that is differentially enriched in various phenotypes of late-stage metastatic prostate cancer. We FACS-purified and transcriptionally profiled basal and luminal epithelial populations from the benign and cancerous regions of primary human prostates. High-throughput RNA sequencing showed the basal population to be defined by genes associated with stem cell signaling programs and invasiveness. Application of a 91-gene basal signature to gene expression datasets from patients with organ-confined or hormone-refractory metastatic prostate cancer revealed that metastatic small cell neuroendocrine carcinoma was molecularly more stem-like than either metastatic adenocarcinoma or organ-confined adenocarcinoma. Bioinformatic analysis of the basal cell and two human small cell gene signatures identified a set of E2F target genes common between prostate small cell neuroendocrine carcinoma and primary prostate basal cells. Taken together, our data suggest that aggressive prostate cancer shares a conserved transcriptional program with normal adult prostate basal stem cells.
National Acad Sciences