Meta-analyses correlating TGF-β/Smad3 target genes with outcome in human breast cancer datasets. Kaplan-Meier analyses were performed using the online GOBO tool to assess the association of the TGF-β-regulated gene sets with distant metastasis-free survival (DMFS) in meta-analyses across multiple breast cancer cohorts (1,379 tumors from eight datasets). Patient datasets were dichotomized to higher than median expression (black) or lower than median expression (grey) of the gene set. P values were determined by the log-rank test. (A,B) Kaplan-Meier plots for survival of all patients in the GOBO datasets, using the set of TGF-β/Smad3 target genes that were uniquely regulated in M3 (the TSTSS). This gene set was designed to be enriched in genes involved in tumor suppression. Weighting (positive or negative) of individual target genes is based on the directionality of TGF-β-regulated gene expression observed in M3 tumors in vivo (A) or in M3 cells in vitro (B) as indicated. (C,D) Correlation of the TSTSS (using the in vivo directional weighting) with DMFS in ER+ (n = 856) (C), and ER- (n = 320) (D) patient subsets of the GOBO cohorts. ns, not significant. ER, estrogen receptor; GOBO, gene expression-based outcome for breast cancer online; TGF-β, transforming growth factor beta; TSS, transcriptional start site; TSTSS, TGF-β/Smad3 tumor suppressor signature.