a simple but highly effective approach to evaluate the prognostic performance of gene expression signatures一个简单但非常有效的方法来评估预后基因表达特征的性能.pdfVIP
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a simple but highly effective approach to evaluate the prognostic performance of gene expression signatures一个简单但非常有效的方法来评估预后基因表达特征的性能
A Simple but Highly Effective Approach to Evaluate the
Prognostic Performance of Gene Expression Signatures
1 2 2 1,3 1
Maud H. W. Starmans *, Glenn Fung , Harald Steck , Bradly G. Wouters , Philippe Lambin
1 Department of Radiation Oncology (Maastro), GROW - School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, The
Netherlands, 2 Department of CAD and Knowledge Solutions, Siemens Medical Solutions, Malvern, Pennsylvania, United States of America, 3 Ontario Cancer Institute/
Princess Margaret Hospital, University Health Network, Toronto, Ontario, Canada
Abstract
Background: Highly parallel analysis of gene expression has recently been used to identify gene sets or ‘signatures’ to
improve patient diagnosis and risk stratification. Once a signature is generated, traditional statistical testing is used to
evaluate its prognostic performance. However, due to the dimensionality of microarrays, this can lead to false interpretation
of these signatures.
Principal Findings: A method was developed to test batches of a user-specified number of randomly chosen signatures in
patient microarray datasets. The percentage of random generated signatures yielding prognostic value was assessed using
ROC analysis by calculating the area under the curve (AUC) in six public available cancer patient microarray datasets. We
found that a signature consisting of randomly selected genes has an average 10% chance of reaching significance when
assessed in a single dataset, but can range from 1% to ,40% depending on the dataset in question. Increasing the number
of validation datasets markedly reduces this number.
Conclusions: We have s
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