Gene expression profiling in rheumatology.

Gene expression profiling in rheumatology.
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风湿病学中的基因表达谱。

DOI:
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发表时间:
2007
期刊:
Methods in Molecular Medicine
影响因子:
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通讯作者:
C. Verweij
C. Verweij
中科院分区:
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文献类型:
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作者:
T. C. van der Pouw Kraan;L. V. van Baarsen;F. Rustenburg;B. Baltus;M. Fero;C. Verweij

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在过去的十年中,组织和细胞中基因表达的分析已经从分析一组选定的基因发展到可能表达的所有基因的高效高通量全基因组筛选方法。复杂的方法学如微阵列技术的发展允许开放式调查,以全面鉴定样品之间差异表达的基因的分数,并定义样品的独特生物学。通过对在不同条件下和疾病期间在个体的细胞和组织中表达的基因进行全面分析,我们可以建立“基因表达谱(签名)”,其表征了在病理生理条件下基因组的动态功能。该策略还提供了将患有复杂异质性疾病的患者细分为更同质的亚组的方法。这种基于发现的研究确定了可能包括功能未知的新基因或先前不知道参与这一过程的基因的生物过程。后一类可能会带来惊喜,有时会促使我们重新思考。我们已经使用微阵列来揭示类风湿关节炎(RA)患者在受影响的滑膜组织的基因表达水平的异质性。不同RA患者滑膜组织的表达谱分析显示了相当大的变异性,导致RA组织至少有两种分子上不同的形式。一种的特征在于指示具有高免疫球蛋白产生的活性炎性浸润的基因,而另一种类型显示出很少的免疫激活,而是显示出更高的基质细胞活性。这些结果证实了类风湿关节炎的异质性,并建议存在不同的致病机制,有助于类风湿关节炎。表达谱的差异提供了基于分子标准对患者进行分层以进行干预治疗的机会。
In the last decade, the analysis of gene expression in tissues and cells has evolved from the analysis of a selected set of genes to an efficient high throughput whole-genome screening approach of potentially all genes expressed. Development of sophisticated methodologies such as microarray technology allows an open-ended survey to identify comprehensively the fraction of genes that are differentially expressed between samples and that define the samples' unique biology. By a global analysis of the genes that are expressed in cells and tissues of an individual under different conditions and during disease, we can build up "gene expression profiles (signatures)" which characterize the dynamic functioning of the genome under pathophysiological conditions. This strategy also provides the means to subdivide patients that suffer from a complex heterogeneous disease into more homogeneous subgroups. Such discovery-based research identifies biological processes that may include new genes with unknown function or genes not previously known to be involved in this process. The latter category may hold surprises that sometimes urge us to redirect our thinking. We have used microarrays to disclose the heterogeneity of rheumatoid arthritis (RA) patients at the level of gene expression of the affected synovial tissues. Analysis of the expression profiles of synovial tissues from different patients with RA revealed considerable variability, resulting in the identification of at least two molecularly distinct forms of RA tissues. One is characterized by genes that indicate an active inflammatory infiltrate with high immunoglobulin production, whereas the other type shows little immune activation and instead shows a higher stromal cell activity. These results confirm the heterogeneous nature of RA and suggest the existence of distinct pathogenic mechanisms that contribute to RA. The differences in expression profiles provide opportunities to stratify patients for intervention therapies based on molecular criteria.
DOI: 10.1073/pnas.96.16.9212
发表时间: 1999-08-03
影响因子: 11.1
作者:
Perou, CM;Jeffrey, SS;Botstein, D
通讯作者: Botstein, D
DOI: 10.1073/pnas.87.5.1663
发表时间: 1990-03-01
影响因子: 11.1
作者:
VANGELDER, RN;VONZASTROW, ME;EBERWINE, JH
通讯作者: EBERWINE, JH