Predictive ability of DNA microarrays for cancer outcomes and correlates: an empirical assessment

被引:234
作者
Ntzani, EE
Ioannidis, JPA [1 ]
机构
[1] Univ Ioannina, Sch Med, Dept Hyg & Epidemiol, Clin & Mol Epidemiol Unit, GR-45110 Ioannina, Greece
[2] Fdn Res & Technol Hellas, Biomed Res Inst, GR-71110 Iraklion, Greece
[3] Tufts Univ, Sch Med, Tufts New England Med Ctr, Div Clin Care Res, Boston, MA 02111 USA
关键词
D O I
10.1016/S0140-6736(03)14686-7
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
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页码:1439 / 1444
页数:6
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