Stem cell and neurogenic gene-expression profiles link prostate basal cells to aggressive prostate cancer.
Stem cell and neurogenic gene-expression profiles link prostate basal cells to aggressive prostate cancer.
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DOI：
10.1038/ncomms10798
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发表时间：
2016-02-29
影响因子：
16.6
通讯作者：
Tang DG
中科院分区：
文献类型：
--
作者：
Zhang D;Park D;Zhong Y;Lu Y;Rycaj K;Gong S;Chen X;Liu X;Chao HP;Whitney P;Calhoun-Davis T;Takata Y;Shen J;Iyer VR;Tang DG
前列腺主要含有基细胞和腔细胞，构成假复层上皮。前列腺上皮转录本的注释为可能影响疾病理解和治疗的发现提供了基础。在这里，我们描述了使用深层RNA测序对人类良性前列腺基底和腔上皮群体进行全基因组转录组分析。通过分子和生物学特征，我们表明不同的基因表达谱解释了它们不同的功能特性。值得注意的是，基底细胞优先表达与干细胞、神经发生和核糖体RNA(RRNA)生物发生相关的基因类别。与这一特征相一致，基底细胞在功能上表现出固有的干细胞样和神经源性特性，并具有增强的rRNA转录活性。与临床相关的是，基底细胞基因表达谱在晚期、间变性、去势抵抗和转移性前列腺癌中丰富。因此，我们将细胞类型特异的基因特征与前列腺癌的侵袭性亚型联系起来，并确定与不良临床特征相关的基因特征。基因表达谱可用于预测癌症患者的预后。在这里，作者描述了人类前列腺上皮细胞谱系的基因表达谱，并表明基底细胞具有固有的干细胞和神经源性属性，在分子上类似于侵袭性前列腺癌。
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. Gene-expression profiles can be used to predict the prognosis of cancer patients. Here, the authors describe gene expression profiles of human prostate epithelial lineages and show that basal cells have intrinsic stem and neurogenic properties, and molecularly resemble aggressive prostate cancer.