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A signature inferred from Drosophila mitotic genes predicts survival of breast cancer patients.

Damasco C, Lembo A, Somma MP, Gatti M, Di Cunto F, Provero P - PLoS ONE (2011)

Bottom Line: 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).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.

View Article: PubMed Central - PubMed

Affiliation: Molecular Biotechnology Center and Department of Genetics, Biology and Biochemistry, University of Turin, Turin, 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 contribution to the predictive power of the DM signature are those involved in cytokinesis.

Conclusion: This finding highlights cytokinesis as an important marker in breast cancer prognosis and as a possible target for antimitotic therapies.

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Comparative evaluation of the prognostic score of the DM                            signature.The prognostic score of the DM signature is compared to those obtained                            from the CIN [15], Proliferation [11], IGS [14],                            Hypoxia [9], 70-gene [3], and Wound [5]                            signatures in the three datasets not used for training. The scores are                            used to predict outcome at five years. The bars show the areas under the                            ROC curves (AUC).
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pone-0014737-g002: Comparative evaluation of the prognostic score of the DM signature.The prognostic score of the DM signature is compared to those obtained from the CIN [15], Proliferation [11], IGS [14], Hypoxia [9], 70-gene [3], and Wound [5] signatures in the three datasets not used for training. The scores are used to predict outcome at five years. The bars show the areas under the ROC curves (AUC).

Mentions: We then compared the DM signature score with the scores of 6 other scalable signatures for performance in predicting cancer outcome at 5 years. For this analysis we used ROC curves generated with the Affymetrix datasets not employed for training (Miller, Sotiriou-Desmedt and Wang). The scores of the CIN [15], Proliferation [11], 70-gene [3], Wound [6], IGS [14], and Hypoxia [9] signatures were computed as described in the respective references, after mapping the genes to the Affymetrix platform (see Methods for details). As shown in Figure 2, the predictive power of the 3 proliferation-based signatures (DM, CIN and Proliferation), measured by the Area Under ROC Curves (AUC), is very similar in all datasets and systematically higher than that of the 70-gene, Wound, IGS, or Hypoxia signature.


A signature inferred from Drosophila mitotic genes predicts survival of breast cancer patients.

Damasco C, Lembo A, Somma MP, Gatti M, Di Cunto F, Provero P - PLoS ONE (2011)

Comparative evaluation of the prognostic score of the DM                            signature.The prognostic score of the DM signature is compared to those obtained                            from the CIN [15], Proliferation [11], IGS [14],                            Hypoxia [9], 70-gene [3], and Wound [5]                            signatures in the three datasets not used for training. The scores are                            used to predict outcome at five years. The bars show the areas under the                            ROC curves (AUC).
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3046113&req=5

pone-0014737-g002: Comparative evaluation of the prognostic score of the DM signature.The prognostic score of the DM signature is compared to those obtained from the CIN [15], Proliferation [11], IGS [14], Hypoxia [9], 70-gene [3], and Wound [5] signatures in the three datasets not used for training. The scores are used to predict outcome at five years. The bars show the areas under the ROC curves (AUC).
Mentions: We then compared the DM signature score with the scores of 6 other scalable signatures for performance in predicting cancer outcome at 5 years. For this analysis we used ROC curves generated with the Affymetrix datasets not employed for training (Miller, Sotiriou-Desmedt and Wang). The scores of the CIN [15], Proliferation [11], 70-gene [3], Wound [6], IGS [14], and Hypoxia [9] signatures were computed as described in the respective references, after mapping the genes to the Affymetrix platform (see Methods for details). As shown in Figure 2, the predictive power of the 3 proliferation-based signatures (DM, CIN and Proliferation), measured by the Area Under ROC Curves (AUC), is very similar in all datasets and systematically higher than that of the 70-gene, Wound, IGS, or Hypoxia signature.

Bottom Line: 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).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.

View Article: PubMed Central - PubMed

Affiliation: Molecular Biotechnology Center and Department of Genetics, Biology and Biochemistry, University of Turin, Turin, 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 contribution to the predictive power of the DM signature are those involved in cytokinesis.

Conclusion: This finding highlights cytokinesis as an important marker in breast cancer prognosis and as a possible target for antimitotic therapies.

Show MeSH
Related in: MedlinePlus