STANDARD_NAME	NADERI_BREAST_CANCER_PROGNOSIS_DN
SYSTEMATIC_NAME	M8629
COLLECTION	C2:CGP
MSIGDB_URL	https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/NADERI_BREAST_CANCER_PROGNOSIS_DN
NAMESPACE	HUMAN_GENE_SYMBOL
DESCRIPTION_BRIEF	Down-regulated genes in the breast cancer prognostic signature of 70 genes that significantly correlated with survival.
DESCRIPTION_FULL	Prognostic signatures in breast cancer derived from microarray expression profiling have been reported by two independent groups. These signatures, however, have not been validated in external studies, making clinical application problematic. We performed microarray expression profiling of 135 early-stage tumors, from a cohort representative of the demographics of breast cancer. Using a recently proposed semisupervised method, we identified a prognostic signature of 70 genes that significantly correlated with survival (hazard ratio (HR): 5.97, 95% confidence interval: 3.0-11.9, P = 2.7e-07). In multivariate analysis, the signature performed independently of other standard prognostic classifiers such as the Nottingham Prognostic Index and the 'Adjuvant!' software. Using two different prognostic classification schemes and measures, nearest centroid (HR) and risk ordering (D-index), the 70-gene classifier was also found to be prognostic in two independent external data sets. Overall, the 70-gene set was prognostic in our study and the two external studies which collectively include 715 patients. In contrast, we found that the two previously described prognostic gene sets performed less optimally in external validation. Finally, a common prognostic module of 29 genes that associated with survival in both our cohort and the two external data sets was identified. In spite of these results, further studies that profile larger cohorts using a single microarray platform, will be needed before prospective clinical use of molecular classifiers can be contemplated.
PMID	16936776
GEOID	E-UCON-1
AUTHORS	Naderi A,Teschendorff AE,Barbosa-Morais NL,Pinder SE,Green AR,Powe DG,Robertson JF,Aparicio S,Ellis IO,Brenton JD,Caldas C
CONTRIBUTOR	Arthur Liberzon
CONTRIBUTOR_ORG	MSigDB Team
EXACT_SOURCE	Table 1
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SOURCE_MEMBERS	ANXA5,C1S,CDV1,CEBPD,CLDN1,CLK4,DCN,FBLN1,MCEE,NANOG,OMD,REXO2,SHOX2,SMOC2,SPARCL1,SSR2,TGFBR3,TXNIP
GENE_SYMBOLS	ANXA5,C1S,IFT81,CEBPD,CLDN1,CLK4,DCN,FBLN1,MCEE,NANOG,OMD,REXO2,SHOX2,SMOC2,SPARCL1,SSR2,TGFBR3,TXNIP
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