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人类癌症的基因表达谱分析。

Gene expression profiling of human cancers.

作者信息

Bucca Giselda, Carruba Giuseppe, Saetta Analisa, Muti Paula, Castagnetta Luigi, Smith Colin P

机构信息

School of Biomedical and Molecular Sciences, University of Surrey, Guildford, GU2 7XH, UK.

出版信息

Ann N Y Acad Sci. 2004 Dec;1028:28-37. doi: 10.1196/annals.1322.003.

Abstract

DNA microarrays allow us to visualize simultaneously the expression of potentially all genes within a cell population or tissue sample-revealing the "transcriptome." The analysis of this type of data is commonly called "gene expression profiling" (GEP) because it provides a comprehensive picture of the pattern of gene expression in a particular biological sample. For this reason microarrays are revolutionizing life sciences research and are leading to the development of novel and powerful methods for investigating cancer biology, classifying cancers, and predicting clinical outcome of cancers. Several recent high-profile reports have revealed how clustering of GEP data can clearly identify clinically (and prognostically) important subtypes of cancer among patients considered by established clinicopathological criteria to have similar tumors. Accurate "prognostic signatures" can be obtained from GEP data, which represent relatively small numbers of genes. These signatures can be valuable in directing appropriate treatment and in predicting clinical outcome, and they generally outperform other systems based on clinical and histological criteria. In this paper the basic principles of DNA microarray technology and the different types of microarray platforms available will be introduced, and the power of the technique will be illustrated by reviewing some recent GEP studies on selected cancers, including a preliminary analysis of hepatocellular carcinoma from our Palermo laboratory. GEP is likely to be adopted in the future as a key decision-making tool in the clinical arena. However, several issues relating to data analysis, reproducibility, cross-comparability, validation, and cost need to be resolved before the technology can be adopted broadly in this context.

摘要

DNA微阵列使我们能够同时可视化细胞群体或组织样本中潜在的所有基因的表达情况,从而揭示“转录组”。对这类数据的分析通常被称为“基因表达谱分析”(GEP),因为它能提供特定生物样本中基因表达模式的全面图景。因此,微阵列正在彻底改变生命科学研究,并推动着用于研究癌症生物学、对癌症进行分类以及预测癌症临床结果的新颖且强大的方法的发展。最近的几份备受瞩目的报告揭示了,对GEP数据进行聚类分析如何能够在那些按照既定临床病理标准被认为患有相似肿瘤的患者中,清晰地识别出临床上(以及预后方面)重要的癌症亚型。从GEP数据中可以获得准确的“预后特征”,这些特征代表的基因数量相对较少。这些特征在指导恰当治疗和预测临床结果方面可能很有价值,而且它们通常比基于临床和组织学标准的其他系统表现更优。在本文中,将介绍DNA微阵列技术的基本原理以及现有的不同类型的微阵列平台,并通过回顾一些近期针对特定癌症的GEP研究(包括我们巴勒莫实验室对肝细胞癌的初步分析)来说明该技术的强大之处。GEP未来可能会被用作临床领域的关键决策工具。然而,在该技术能够在这一背景下被广泛应用之前,与数据分析、可重复性、交叉可比性、验证以及成本相关的几个问题需要得到解决。

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