Segal Eran, Friedman Nir, Koller Daphne, Regev Aviv
Computer Science Department, Stanford University, Stanford, California 94305, USA.
Nat Genet. 2004 Oct;36(10):1090-8. doi: 10.1038/ng1434. Epub 2004 Sep 26.
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.
DNA微阵列被广泛用于研究肿瘤中基因表达的变化，但此类研究通常是针对特定系统的，并未涉及不同类型肿瘤之间的共性和差异。在此，我们对涵盖22种肿瘤类型的1975篇已发表的微阵列进行了综合分析。我们根据模块（协同发挥特定功能的基因集）的行为来描述不同肿瘤中的表达谱。通过简单的统一分析，我们提取了模块，并将肿瘤中的基因表达谱表征为激活和失活模块的组合。某些模块的激活特定于特定类型的肿瘤；例如，一个生长抑制模块在急性淋巴细胞白血病中被特异性抑制，这可能是这些癌症中增殖失控的基础。其他模块在多种临床情况下都有出现，提示存在共同的肿瘤进展机制。例如，骨成骨细胞模块跨越多种肿瘤类型，包括分泌型生长因子及其受体。我们的研究结果表明，原发性肿瘤增殖和骨转移存在单一机制。我们的分析为诊断、预后和治疗研究提供了多个研究方向。
