Stem cell and neurogenic gene-expression profiles link prostate basal cells to aggressive prostate cancer

Dingxiao Zhang (), Daechan Park, Yi Zhong, Yue Lu, Kiera Rycaj, Shuai Gong, Xin Chen, Xin Liu, Hsueh-Ping Chao, Pamela Whitney, Tammy Calhoun-Davis, Yoko Takata, Jianjun Shen, Vishwanath R. Iyer and Dean G. Tang ()
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Dingxiao Zhang: University of Texas MD Anderson Cancer Center
Daechan Park: Institute for Cellular and Molecular Biology, Center for Systems and Synthetic Biology, University of Texas at Austin
Yi Zhong: University of Texas MD Anderson Cancer Center
Yue Lu: University of Texas MD Anderson Cancer Center
Kiera Rycaj: University of Texas MD Anderson Cancer Center
Shuai Gong: University of Texas MD Anderson Cancer Center
Xin Chen: University of Texas MD Anderson Cancer Center
Xin Liu: University of Texas MD Anderson Cancer Center
Hsueh-Ping Chao: University of Texas MD Anderson Cancer Center
Pamela Whitney: University of Texas MD Anderson Cancer Center
Tammy Calhoun-Davis: University of Texas MD Anderson Cancer Center
Yoko Takata: University of Texas MD Anderson Cancer Center
Jianjun Shen: University of Texas MD Anderson Cancer Center
Vishwanath R. Iyer: Institute for Cellular and Molecular Biology, Center for Systems and Synthetic Biology, University of Texas at Austin
Dean G. Tang: University of Texas MD Anderson Cancer Center

Nature Communications, 2016, vol. 7, issue 1, 1-15

Abstract: Abstract The prostate gland mainly contains basal and luminal cells constructed as a pseudostratified epithelium. Annotation of prostate epithelial transcriptomes provides a foundation for discoveries that can impact disease understanding and treatment. Here we describe a genome-wide transcriptome analysis of human benign prostatic basal and luminal epithelial populations using deep RNA sequencing. Through molecular and biological characterizations, we show that the differential gene-expression profiles account for their distinct functional properties. Strikingly, basal cells preferentially express gene categories associated with stem cells, neurogenesis and ribosomal RNA (rRNA) biogenesis. Consistent with this profile, basal cells functionally exhibit intrinsic stem-like and neurogenic properties with enhanced rRNA transcription activity. Of clinical relevance, the basal cell gene-expression profile is enriched in advanced, anaplastic, castration-resistant and metastatic prostate cancers. Therefore, we link the cell-type-specific gene signatures to aggressive subtypes of prostate cancer and identify gene signatures associated with adverse clinical features.

Date: 2016
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DOI: 10.1038/ncomms10798

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