Predictive ability of DNA microarrays for cancer outcomes and correlates: an empirical assessment
Predictive ability of DNA microarrays for cancer outcomes and correlates: an empirical assessment
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DOI：
10.1016/s0140-6736(03)14686-7
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发表时间：
2003-11-01
期刊：
影响因子：
168.9
通讯作者：
Ioannidis, JPA
中科院分区：
文献类型：
--
作者：
Ntzani, EE;Ioannidis, JPA
背景DNA微阵列被用于许多应用，包括通过同时分析数千个基因的表达来预测癌症结果。我们系统地评估了这种方法的预测性能的主要临床结果（死亡，转移，复发，对治疗的反应）和相关性的基因分析与其他临床病理相关的恶性disorders.Methods合格的报告检索MEDLINE（1995年至2003年4月）进行了评估的功能的研究设计，报告的预测性能，并考虑到其他预后因素。我们寻找研究变量，增加的机会，一个显着的相关性与临床结果或correlate将被发现。结果84个合格的研究，其中30个主要的临床结果。纳入了中位25例（IQR 15-45）癌症患者。在主要临床结局的研究中，有9项进行了交叉验证，但只有2项完成; 6项研究使用了监督预测模型的独立验证。较小的研究比较大的研究显示出更好的临床结果的敏感性和特异性。只有11项针对主要临床结局的研究进行了其他预后因素的亚组或调整分析。在所有84项研究中，显著相关性是样本量每增加一倍的3.5倍（95%CI 1.5-8.0），微阵列探针每增加10倍的9.7倍（2.0-47.0）。具有适当临床设计的大型研究，已知预测因子的调整和适当的验证对于这种非常有前途的技术至关重要。
Background DNA microarrays are being used for many applications, including the prediction of cancer outcomes by simultaneous analysis of the expression of thousands of genes. We systematically assessed the predictive performance of this method for major clinical outcomes (death, metastasis, recurrence, response to therapy) and the correlation of gene profiling with other clinicopathological correlates of malignant disorders.Methods Eligible reports retrieved from MEDLINE (1995 to April, 2003) were assessed for features of study design, reported predictive performance, and consideration of other prognostic factors. We searched for study variables that increased the chances that a significant association with a clinical outcome or correlate would be found.Findings 84 eligible studies were identified, of which 30 addressed major clinical outcomes. A median of 25 (IQR 15-45) patients with cancer were included. Among the studies of major clinical outcomes, nine did cross-validation but it was complete in only two of them; six studies used independent validation of supervised predictive models. Smaller studies showed better sensitivity and specificity for clinical outcomes than larger studies. Only 11 studies addressing major clinical outcomes did subgroup or adjusted analyses for other prognostic factors. Across all 84 studies, significant associations were 3.5 (95% CI 1.5-8.0) times more likely per doubling of sample size and 9.7 (2.0-47.0) times more likely per ten-fold increase in microarray probes.Interpretation DNA microarrays addressing cancer outcomes show variable prognostic performance. Larger studies with appropriate clinical design, adjustment for known predictors, and proper validation are essential for this highly promising technology.