Outcome signature genes in breast cancer: is there a unique set?
BACKGROUND
Predicting the metastatic potential of primary malignant tissues has direct bearing on the choice of therapy. Several microarray studies yielded gene sets whose expression profiles successfully predicted survival. Nevertheless, the overlap between these gene sets is almost zero. Such small overlaps were observed also in other complex diseases, and the variables that could account for the differences had evoked a wide interest. One of the main open questions in this context is whether the disparity can be attributed only to trivial reasons such as different technologies, different patients and different types of analyses.


RESULTS
To answer this question, we concentrated on a single breast cancer dataset, and analyzed it by a single method, the one which was used by van't Veer et al. to produce a set of outcome-predictive genes. We showed that, in fact, the resulting set of genes is not unique; it is strongly influenced by the subset of patients used for gene selection. Many equally predictive lists could have been produced from the same analysis. Three main properties of the data explain this sensitivity: (1) many genes are correlated with survival; (2) the differences between these correlations are small; (3) the correlations fluctuate strongly when measured over different subsets of patients. A possible biological explanation for these properties is discussed.


BACKGROUND
eytan.domany@weizmann.ac.il


BACKGROUND
http://www.weizmann.ac.il/physics/complex/compphys/downloads/liate/
Ein-Dor
Liat
L
Department of Physics of Complex Systems, Weizmann Institute of Science Rehovot 76100, Israel.
Kela
Itai
I
Getz
Gad
G
Givol
David
D
Domany
Eytan
E
D014408:Biomarkers, Tumor / Q000235:genetics*; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality; D002986:Clinical Trials as Topic; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D015972:Gene Expression Regulation, Neoplastic; D005820:Genetic Testing / Q000379:methods*; D014644:Genetic Variation; D006801:Humans; D009363:Neoplasm Proteins / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D011379:Prognosis; D015203:Reproducibility of Results; D018401:Sample Size; D012680:Sensitivity and Specificity; D016019:Survival Analysis; D016896:Treatment Outcome
D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins