CCL171, T47D, MDA-MB231 cell lines: stimulation with BMP7 and antagonists. Homo sapiens

Methods: We used an ex vivo culture model and measured gene expression changes in human lung fibroblasts after stimulation with BMPs and their antagonists using HEEBO microarrays. The in vitro data were correlated with in vivo observations in published expression datasets of human lung adenocarcinomas. Results: We have systematically analyzed the response to BMP2, BMP4, BMP7 and their antagonists, gremlin and noggin, to define common and specific gene expression patterns. A BMP2 induced gene expression signature was defined, which is specific for stromal fibroblasts. Gene expression profiles from lung adenocarcinoma biopsies were analyzed to determine the prognostic significance of the Fibroblast specific BMP2 induced gene list. This gene list successfully segregated patients with different prognostic outcome in 3 datasets. In a small dataset (Garber et al.) there was a strong trend for a worse prognosis of patients with adenocarcinomas of all stages over-expressing the Fibroblast specific BMP2 induced gene list. In two larger datasets with stage I adenocarcinomas we observed a significantly worse disease-free (p=0.002, Lee et al. and p=0.002, Bhattacharjee et al.) and overall survival (p=0.0002). Conclusions: The effects of BMPs and their antagonists are heterogeneous in different cell types. The gene expression pattern induced by BMP2 in primary lung fibroblasts may predict outcomes of patients with lung adenocarcinomas. A stimulus or stress experiment design type is where that tests response of an organism(s) to stress/stimulus. e.g. osmotic stress, behavioral treatment Overall design: stimulus_or_stress_design

方法：本研究采用离体培养模型，借助HEEBO微阵列（HEEBO microarrays）检测骨形态发生蛋白（Bone Morphogenetic Proteins, BMPs）及其拮抗剂刺激后人肺成纤维细胞的基因表达变化情况，并将体外实验数据与已发表的人肺腺癌表达数据集的体内观测结果进行关联分析。
结果：本研究系统分析了人肺成纤维细胞对骨形态发生蛋白2（Bone Morphogenetic Protein 2, BMP2）、骨形态发生蛋白4（Bone Morphogenetic Protein 4, BMP4）、骨形态发生蛋白7（Bone Morphogenetic Protein 7, BMP7）及其拮抗剂GREMLIN、NOGGIN的应答反应，以明确其共同与特异性基因表达模式。本研究界定了一种由BMP2诱导的、基质成纤维细胞特异性的基因表达特征。通过分析肺腺癌活检组织的基因表达谱，探究成纤维细胞特异性BMP2诱导基因列表的预后价值。该基因列表可在3个独立数据集中有效区分预后结局不同的肺腺癌患者。在小型数据集（Garber等）中，过表达该成纤维细胞特异性BMP2诱导基因列表的各分期肺腺癌患者呈现出不良预后的显著趋势。在两个包含Ⅰ期肺腺癌的大型数据集中，过表达该基因列表的患者无病生存期（Lee等：P=0.002；Bhattacharjee等：P=0.002）与总生存期（P=0.0002）均显著更差。
结论：BMPs及其拮抗剂在不同细胞类型中的生物学效应具有异质性。原代肺成纤维细胞中BMP2诱导的基因表达模式可有效预测肺腺癌患者的预后结局。
刺激或应激实验设计类型指用于检测生物体对应激或刺激的应答反应的实验设计类型，例如渗透压应激、行为干预。
实验设计概述：stimulus_or_stress_design