In silico dissection of cell-type-associated patterns of gene expression in prostate cancer
In silico dissection of cell-type-associated patterns of gene expression in prostate cancer
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DOI：
10.1073/pnas.2536479100
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发表时间：
2004-01-13
影响因子：
11.1
通讯作者：
Mercola, D
中科院分区：
文献类型：
--
作者：
Stuart, RO;Wachsman, W;Mercola, D
前列腺癌是由恶性细胞和非恶性细胞混合并相互作用而成的复杂实体。然而，通过标准基因表达谱进行分子分析是有限的，因为空间信息和非肿瘤细胞类型在样品制备过程中丢失。我们对88例前列腺标本进行了肿瘤、良性增生性上皮、间质和扩张的囊腺的相对含量评分。然后将这些细胞类型的比例与微阵列分析确定的基因表达水平联系起来，揭示出独特的细胞特异性图谱。恶性和非恶性上皮细胞(肿瘤和良性增生性上皮)的基因表达差异可以被识别，而不会被主导许多样本的基质的贡献所混淆，也不会牺牲可能的旁分泌影响。免疫组织化学和定量聚合酶链式反应验证所选基因的细胞特异性表达。这些结果为这三个谱系提供了与发病、诊断和治疗相关的基因表达模式。
Prostate tumors are complex entities composed of malignant cells mixed and interacting with nonmalignant cells. However, molecular analyses by standard gene expression profiling are limited because spatial information and nontumor cell types are lost in sample preparation. We scored 88 prostate specimens for relative content of tumor, benign hyperplastic epithelium, stroma, and dilated cystic glands. The proportions of these cell types were then linked in silico to gene expression levels determined by microarray analysis, revealing unique cell-specific profiles. Gene expression differences for malignant and nonmalignant epithelial cells (tumor versus benign hyperplastic epithelium) could be identified without being confounded by contributions from stroma that dominate many samples or sacrificing possible paracrine influences. Cell-specific expression of selected genes was validated by immunohistochemistry and quantitative PCR. The results provide patterns of gene expression for these three lineages with relevance to pathogenetic, diagnostic, and therapeutic considerations.