a signature inferred from drosophila mitotic genes predicts survival of breast cancer patients签名推断从果蝇有丝分裂基因预测乳腺癌患者的生存.pdfVIP
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a signature inferred from drosophila mitotic genes predicts survival of breast cancer patients签名推断从果蝇有丝分裂基因预测乳腺癌患者的生存
A Signature Inferred from Drosophila Mitotic Genes
Predicts Survival of Breast Cancer Patients
1 1 2 2 1
Christian Damasco , Antonio Lembo , Maria Patrizia Somma , Maurizio Gatti , Ferdinando Di Cunto ,
Paolo Provero1*
1 Molecular Biotechnology Center and Department of Genetics, Biology and Biochemistry, University of Turin, Turin, Italy, 2 Dipartimento di Biologia e Biotecnologie, and
`
Istituto di Biologia e Patologia Molecolari del CNR, ‘‘Sapienza’’ Universita di Roma, Roma, Italy
Abstract
Introduction: The classification of breast cancer patients into risk groups provides a powerful tool for the identification of
patients who will benefit from aggressive systemic therapy. The analysis of microarray data has generated several gene
expression signatures that improve diagnosis and allow risk assessment. There is also evidence that cell proliferation-related
genes have a high predictive power within these signatures.
Methods: We thus constructed a gene expression signature (the DM signature) using the human orthologues of 108
Drosophila melanogaster genes required for either the maintenance of chromosome integrity (36 genes) or mitotic division
(72 genes).
Results: The DM signature has minimal overlap with the extant signatures and is highly predictive of survival in 5 large
breast cancer datasets. In addition, we show that the DM signature outperforms many widely used breast cancer signatures
in predictive power, and performs comparably to other proliferation-based signatures. For most genes of the DM signature,
an increased expression is negatively correlated with patient survival. The genes that provide the highest con
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