A module map showing conditional activity of expression modules in cancer
A module map showing conditional activity of expression modules in cancer
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DOI：
10.1038/ng1434
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发表时间：
2004-10-01
期刊：
影响因子：
30.8
通讯作者：
Regev, A
中科院分区：
文献类型：
--
作者：
Segal, E;Friedman, N;Regev, A
DNA微阵列被广泛用于研究肿瘤中基因表达的变化，但此类研究通常是系统特异性的，不能解决不同类型肿瘤之间的共性和差异。在这里，我们提出了一个综合分析1,975发表的微阵列跨越22种肿瘤类型。我们根据模块的行为描述了不同肿瘤中的表达谱，这些模块是一组基因，它们共同发挥特定的功能。使用一个简单的统一的分析，我们提取模块和特征的基因表达谱在肿瘤中的激活和失活模块的组合。某些模块的激活对特定类型的肿瘤是特异性的;例如，生长抑制模块在急性淋巴细胞白血病中被特异性抑制，并且可能是这些癌症中增殖失调的基础。其他模块在不同的临床条件下共享，提示常见的肿瘤进展机制。例如，骨成骨细胞模块跨越多种肿瘤类型，包括分泌的生长因子及其受体。我们的研究结果表明，有一个单一的机制，既原发肿瘤增殖和转移到骨。我们的分析为诊断、预后和治疗研究提供了多个研究方向。
DNA microarrays are widely used to study changes in gene expression in tumors, but such studies are typically system-specific and do not address the commonalities and variations between different types of tumor. Here we present an integrated analysis of 1,975 published microarrays spanning 22 tumor types. We describe expression profiles in different tumors in terms of the behavior of modules, sets of genes that act in concert to carry out a specific function. Using a simple unified analysis, we extract modules and characterize gene-expression profiles in tumors as a combination of activated and deactivated modules. Activation of some modules is specific to particular types of tumor; for example, a growth-inhibitory module is specifically repressed in acute lymphoblastic leukemias and may underlie the deregulated proliferation in these cancers. Other modules are shared across a diverse set of clinical conditions, suggestive of common tumor progression mechanisms. For example, the bone osteoblastic module spans a variety of tumor types and includes both secreted growth factors and their receptors. Our findings suggest that there is a single mechanism for both primary tumor proliferation and metastasis to bone. Our analysis presents multiple research directions for diagnostic, prognostic and therapeutic studies.