Stuart Robert O, Wachsman William, Berry Charles C, Wang-Rodriguez Jessica, Wasserman Linda, Klacansky Igor, Masys Dan, Arden Karen, Goodison Steven, McClelland Michael, Wang Yipeng, Sawyers Anne, Kalcheva Iveta, Tarin David, Mercola Dan
Veterans Affairs San Diego Healthcare System, and Department of Medicine and John and Rebecca Moores UCSD Cancer Center, University of California at San Diego, La Jolla, USA.
Proc Natl Acad Sci U S A. 2004 Jan 13;101(2):615-20. doi: 10.1073/pnas.2536479100.
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.
前列腺肿瘤是由恶性细胞与非恶性细胞混合并相互作用构成的复杂实体。然而，通过标准基因表达谱进行的分子分析存在局限性，因为在样本制备过程中会丢失空间信息和非肿瘤细胞类型。我们对88个前列腺标本的肿瘤、良性增生上皮、基质和扩张性囊性腺体的相对含量进行了评分。然后，通过计算机模拟将这些细胞类型的比例与通过微阵列分析确定的基因表达水平联系起来，揭示了独特的细胞特异性谱。可以识别恶性和非恶性上皮细胞（肿瘤与良性增生上皮）之间的基因表达差异，而不会受到在许多样本中占主导地位的基质的影响，也无需牺牲可能的旁分泌影响。通过免疫组织化学和定量PCR验证了所选基因的细胞特异性表达。这些结果提供了这三个谱系的基因表达模式，与发病机制、诊断和治疗方面的考虑相关。
