A signature inferred from Drosophila mitotic genes predicts survival of breast cancer patients |
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Authors: | Damasco Christian Lembo Antonio Somma Maria Patrizia Gatti Maurizio Di Cunto Ferdinando Provero Paolo |
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Institution: | Molecular Biotechnology Center and Department of Genetics, Biology and Biochemistry, University of Turin, Turin, Italy. |
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Abstract: | IntroductionThe 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.MethodsWe 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).ResultsThe 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 contribution to the predictive power of the
DM signature are those involved in cytokinesis.ConclusionThis finding highlights cytokinesis as an important marker in breast cancer
prognosis and as a possible target for antimitotic therapies. |
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