The macrophage colony-stimulating factor 1 response signature in breast carcinoma.
The macrophage colony-stimulating factor 1 response signature in breast carcinoma.
复制标题
DOI：
10.1158/1078-0432.ccr-08-1283
复制
发表时间：
2009-02-01
期刊：
影响因子：
--
通讯作者：
West RB
中科院分区：
文献类型：
--
作者：
Beck AH;Espinosa I;Edris B;Li R;Montgomery K;Zhu S;Varma S;Marinelli RJ;van de Rijn M;West RB
巨噬细胞在乳腺癌中起着重要的作用这项研究是为了定义一种新型的CSF1反应签名，并评估其在乳腺癌中的临床和生物学意义。
我们通过鉴定弯曲型巨型细胞肿瘤中过表达的基因和小猪虫滑膜炎（主要由巨噬细胞组成的巨噬细胞，响应于CSF1的过表达）来定义CSF1反应签名。我们在乳腺癌中的签名，分析了八个已发表的乳腺癌基因表达数据集（n = 982）中CSF1反应签名基因的表达，并进行了免疫组织化学以及对乳腺癌组织微阵列上CSF1反应基因的原位杂交基因（n = 283）。
在基因微阵列和组织微阵列分析中，乳腺癌的一致亚群（17-25％）表明CSF1反应签名与较高的肿瘤级相关，雌激素受体的表达降低，孕激素受体的表达降低和降低p53突变增加（p <0.001）。
我们的数据表明，在乳腺癌的一部分中，CSF1反应签名始终可见，并且与肿瘤的生物学特征相关。有针对性的治疗。
Macrophages play an important role in breast carcinogenesis. The pathways that mediate the macrophage contribution to breast cancer and the heterogeneity that exists within macrophages are incompletely understood. Macrophage colony stimulating factor-1 (CSF1) is the primary regulator of tissue macrophages. The purpose of this study was to define a novel CSF1 response signature and to evaluate its clinical and biological significance in breast cancer. We defined the CSF1 response signature by identifying genes overexpressed in tenosynovial giant cell tumor and pigmented villonodular synovitis (tumors composed predominantly of macrophages recruited in response to the overexpression of CSF1) as compared with desmoid type fibromatosis and solitary fibrous tumor. To characterize the CSF1 response signature in breast cancer, we analyzed the expression of CSF1 response signature genes in eight published breast cancer gene expression datasets (n=982) and performed immunohistochemistry and in situ hybridization for CSF1 response genes on a breast cancer tissue microarray (n=283). In both the gene microarray and tissue microarray analyses, a consistent subset (17–25%) of breast cancers shows the CSF1 response signature. The signature is associated with higher tumor grade, decreased expression of estrogen receptor, decreased expression of progesterone receptor, and increased p53 mutations (p <0.001). Our data show that the CSF1 response signature is consistently seen in a subset of breast carcinomas and correlates with biological features of the tumor. Our findings provide insight into macrophage biology and may facilitate the development of personalized therapy for patients most likely to benefit from CSF1-targeted treatments.