A basal stem cell signature identifies aggressive prostate cancer phenotypes

Area of Science:

• Oncology
• Stem Cell Biology
• Genomics

Background:

• Cancer aggressiveness correlates with stem cell properties and activated signaling pathways.
• Variations in stemness and transcriptional similarity to normal stem cells across late-stage cancer subtypes remain unclear.
• Prostate cancer subtypes may differ in their stemness characteristics.

Purpose of the Study:

• To identify a gene signature for human prostate basal cells.
• To investigate the enrichment of this signature in various late-stage metastatic prostate cancer phenotypes.
• To compare the stemness properties of different prostate cancer subtypes.

Main Methods:

• Fluorescence-activated cell sorting (FACS) purification of basal and luminal epithelial cells from benign and cancerous prostate tissues.
• High-throughput RNA sequencing to profile gene expression.
• Application of a 91-gene basal signature to patient gene expression datasets.
• Bioinformatic analysis of gene signatures.

Main Results:

• Prostate basal cells are characterized by genes associated with stem cell signaling and invasiveness.
• A 91-gene basal signature was enriched in metastatic prostate cancer.
• Metastatic small cell neuroendocrine carcinoma displayed more stem-like molecular features than adenocarcinoma subtypes.
• A common set of E2F target genes was identified between prostate small cell neuroendocrine carcinoma and basal stem cells.

Conclusions:

• Aggressive prostate cancer shares a conserved transcriptional program with normal adult prostate basal stem cells.
• Prostate basal cells possess stemness properties relevant to cancer progression.
• Small cell neuroendocrine prostate cancer represents a highly stem-like subtype.