期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 112, 期 47, 页码 E6544-E6552出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1518007112
关键词
RNA-seq; prostate cancer; stem cell signature; basal cell; neuroendocrine prostate cancer
资金
- UCLA Tumor Immunology Training Program [T32 CA009120]
- NIH [U24-CA143858]
- Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research
- Stand up to Cancer/American Association for Cancer Research/Prostate Cancer Foundation Grant [SU2C-AACR-DT0812]
- Movember Foundation
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.
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