title: Stem cell and neurogenic gene-expression profiles link prostate basal cells to aggressive prostate cancer.
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.
authors.affiliation: Department of Epigenetics and Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Smithville, 78957 Texas, USA.
authors.forename: Dingxiao
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Department of Molecular Biosciences, Institute for Cellular and Molecular Biology, Center for Systems and Synthetic Biology, University of Texas at Austin, Austin, 78712 Texas, USA.
authors.forename: Daechan
authors.identifier: http://orcid.org/0000-0003-4991-5247
authors.initials: D
authors.lastname: Park
authors.affiliation: Department of Epigenetics and Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Smithville, 78957 Texas, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhong
authors.affiliation: Department of Epigenetics and Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Smithville, 78957 Texas, USA.
authors.forename: Yue
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Epigenetics and Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Smithville, 78957 Texas, USA.
authors.forename: Kiera
authors.initials: K
authors.lastname: Rycaj
authors.affiliation: Department of Epigenetics and Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Smithville, 78957 Texas, USA.
authors.forename: Shuai
authors.initials: S
authors.lastname: Gong
authors.affiliation: Department of Epigenetics and Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Smithville, 78957 Texas, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Epigenetics and Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Smithville, 78957 Texas, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Epigenetics and Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Smithville, 78957 Texas, USA.
authors.forename: Hsueh-Ping
authors.initials: HP
authors.lastname: Chao
authors.affiliation: Department of Epigenetics and Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Smithville, 78957 Texas, USA.
authors.forename: Pamela
authors.initials: P
authors.lastname: Whitney
authors.affiliation: Department of Epigenetics and Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Smithville, 78957 Texas, USA.
authors.forename: Tammy
authors.initials: T
authors.lastname: Calhoun-Davis
authors.affiliation: Department of Epigenetics and Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Smithville, 78957 Texas, USA.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Takata
authors.affiliation: Department of Epigenetics and Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Smithville, 78957 Texas, USA.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Shen
authors.affiliation: Department of Molecular Biosciences, Institute for Cellular and Molecular Biology, Center for Systems and Synthetic Biology, University of Texas at Austin, Austin, 78712 Texas, USA.
authors.forename: Vishwanath R
authors.initials: VR
authors.lastname: Iyer
authors.affiliation: Department of Epigenetics and Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Smithville, 78957 Texas, USA.|Cancer Stem Cell Institute, Research Center for Translational Medicine, East Hospital, Tongji University School of Medicine, 2001120 Shanghai, China.|Centers for Cancer Epigenetics, Stem Cell and Developmental Biology, RNA Interference and Non-Coding RNAs and Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Houston, 77030 Texas, USA.
authors.forename: Dean G
authors.initials: DG
authors.lastname: Tang
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism; D015415:Biomarkers; D019070:Cell Lineage; D005786:Gene Expression Regulation / Q000502:physiology*; D055785:Gene Knockdown Techniques; D006801:Humans; D008297:Male; D011467:Prostate / Q000166:cytology*; D011471:Prostatic Neoplasms / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D012335:RNA, Ribosomal / Q000235:genetics / Q000378:metabolism; D012270:Ribosomes / Q000378:metabolism; D013234:Stem Cells / Q000502:physiology*; D059467:Transcriptome
chemical_list: D015415:Biomarkers; C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; D012335:RNA, Ribosomal