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

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

DAMASCO, CHRISTIAN;LEMBO, ANTONIO;DI CUNTO, Ferdinando;PROVERO, Paolo
2011

Abstract

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.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).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.This finding highlights cytokinesis as an important marker in breast cancer prognosis and as a possible target for antimitotic therapies.
6
e14737
00
http://dx.doi.org/10.1371/journal.pone.0014737
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3046113/pdf/pone.0014737.pdf
breast cancer
Damasco C; Lembo A; Somma MP; Gatti M; Di Cunto F; Provero P
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2318/91590
Citazioni
  • ???jsp.display-item.citation.pmc??? 6
  • Scopus 9
  • ???jsp.display-item.citation.isi??? 8
social impact