Prognosis of breast cancer and gene expression profiling using DNA arrays
Prognosis of breast cancer and gene expression profiling using DNA arrays
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DOI：
10.1111/j.1749-6632.2002.tb05954.x
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发表时间：
2002-01-01
期刊：
影响因子：
--
通讯作者：
Nguyen, C
中科院分区：
文献类型：
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作者：
Bertucci, F;Houlgatte, R;Nguyen, C
乳腺癌是一种复杂的遗传疾病，其特征是多种分子改变的积累。由此产生的临床异质性使得目前基于临床病理因素的治疗策略不能完全适应每位患者。今天，DNA阵列可以同时定量分析数千个基因的mRNA表达水平，为解决这种复杂性提供了新的工具。在癌症领域的潜在应用是多方面的，初步的研究结果是有希望的。利用自制的DNA阵列，我们确定了一组23个基因的预测因子，这些基因的表达模式区分了两组乳腺癌患者在辅助化疗后的不同生存率。然后，我们在一个更大的、独立的、同质的、接受蒽环类辅助化疗治疗的预后差的原发性乳腺癌中验证并进一步扩展了这些结果。我们证实了23个基因集预测器提供的预后分类。然后，我们改进了预测集，并通过将肿瘤分为三种长期生存率显著不同的类别来改进分类。这些结果显示了该技术的潜力，为学术研究团队提供了一种可访问的方法。我们还表明，尼龙DNA阵列与放射性检测具有优异的灵敏度，在临床情况下，可用材料的数量是有限的优势。
Breast cancer is a complex genetic disease characterized by the accumulation of multiple molecular alterations. The resulting clinical heterogeneity makes current therapeutic strategies-based on clinicopathlogical factors-less than perfectly adapted to each patient. Today, DNA arrays, by allowing the simultaneous and quantitative analysis of the mRNA expression levels of thousands of genes in a single assay, provide novel tools to tackle this complexity. Potential applications are multiple in the cancer field and the first research results are promising. Using home-made DNA arrays in an approach easily compatible with academic research-nylon support and radioactive detection-we identified a predictor set of 23 genes whose expression patterns differentiated two groups of breast cancer patients with different survival after adjuvant chemotherapy. We then validated and further extended these results in a larger, independent and homogeneous series of poor prognosis primary breast cancers treated with adjuvant anthracyclin-based chemotherapy. We confirmed the prognostic classification provided by the 23-gene set predictor. We then improved the predictor set and refined the classification by sorting the tumors into three classes with significantly different long-term survival. These results show the potential of the technology with an accessible approach for academic research teams. We also showed that nylon DNA arrays with radioactive detection are associated with excellent sensitivity, an advantage in clinical situations where the amount of available material is limited.