Determination of stromal signatures in breast carcinoma.
Determination of stromal signatures in breast carcinoma.
复制标题
确定乳腺癌中基质特征的测定。
DOI：
10.1371/journal.pbio.0030187
复制
发表时间：
2005-06
期刊：
影响因子：
9.8
通讯作者：
中科院分区：
文献类型：
--
作者：
许多软组织肿瘤具有正常结缔组织的特征。我们假设不同类型的成纤维细胞肿瘤代表不同的成纤维细胞群体或这些细胞的不同激活状态。我们通过DNA微阵列分析研究了两种具有成纤维细胞特征的肿瘤，孤立性纤维瘤（SFT）和韧带样型纤维瘤病（DTF），发现它们具有非常不同的表达谱，包括细胞外基质基因和生长因子表达模式的显着差异。利用免疫组化和原位杂交的组织芯片，我们发现，这两种肿瘤的基因有相互特异性表达的非肿瘤组织间质。我们定义了一组786个基因点，其表达模式将SFT与DTF区分开来。在对295个先前发表的乳腺癌的DNA微阵列基因表达数据的分析中，我们发现该基因集的表达定义了两组在总生存率方面具有显著差异的乳腺癌。其中一组具有有利的结果，并通过DTF基因的表达来定义。另一组肿瘤预后差，并显示出丰富的SFT型基因的可变表达。我们的研究结果表明，宿主间质反应显着不同的癌和软组织肿瘤的基因表达模式的特点，可以用来发现新的正常结缔组织细胞的标志物。作者使用两种不同的成纤维细胞肿瘤来鉴定由正常基质细胞（身体组织和/或肿瘤的支撑框架）表达的标记物，并表明不同的基质背景存在于不同的乳腺癌中。
Many soft tissue tumors recapitulate features of normal connective tissue. We hypothesize that different types of fibroblastic tumors are representative of different populations of fibroblastic cells or different activation states of these cells. We examined two tumors with fibroblastic features, solitary fibrous tumor (SFT) and desmoid-type fibromatosis (DTF), by DNA microarray analysis and found that they have very different expression profiles, including significant differences in their patterns of expression of extracellular matrix genes and growth factors. Using immunohistochemistry and in situ hybridization on a tissue microarray, we found that genes specific for these two tumors have mutually specific expression in the stroma of nonneoplastic tissues. We defined a set of 786 gene spots whose pattern of expression distinguishes SFT from DTF. In an analysis of DNA microarray gene expression data from 295 previously published breast carcinomas, we found that expression of this gene set defined two groups of breast carcinomas with significant differences in overall survival. One of the groups had a favorable outcome and was defined by the expression of DTF genes. The other group of tumors had a poor prognosis and showed variable expression of genes enriched for SFT type. Our findings suggest that the host stromal response varies significantly among carcinomas and that gene expression patterns characteristic of soft tissue tumors can be used to discover new markers for normal connective tissue cells. The authors used two different fibroblastic tumors to identify markers expressed by normal stroma cells (the supporting framework of body tissues and/or tumors), and show that different stromal backgrounds exist in different breast carcinomas.