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Fig. 6 | BMC Medical Genomics

Fig. 6

From: RNA-seq from archival FFPE breast cancer samples: molecular pathway fidelity and novel discovery

Fig. 6

Regulon Validation of FFPE RNA-seq for pathway discovery reveals KDM4B as potential predictor of outcomes in ER+ TCGA breast cancer cohort. An established breast cancer regulon composed from The Cancer Genome Atlas (TCGA) specimens was utilized to interrogate differential signaling in transcription networks between ER+ and ER- samples from both FFPE and fresh specimen cohorts. a The 30 most differentially active regulons between ER+ and ER- samples in fresh (left) and FFPE (right) specimens are displayed. Shared regulons are shown in white boxes, and fresh vs. FFPE specific regulons are shown in orange. The activity (Act) of the regulon is displayed (red and blue for high and low network activity, respectively), as is the gene expression (Exp) of the transcription factor itself. b Plotting regulon (n = 5000) expression levels (Ranks) reveals high level of correlation between fresh and FFPE samples, whereas c) single-gene analysis (n = 14,330) reveals reduced correlation between fresh and FFPE. d Single-sample regulon activity scores were plotted in TCGA breast cancer cases annotated by IHC as ER+ (red, n = 478) or ER- (blue, n = 153) for each of the top 4 upregulated and downregulated regulons from the regulon analysis, depicting significant (****, p < .0001, Welch’s unpaired, two tailed, t-test) differences between ER+ and ER- samples and independently validating regulons results. e Five year survival probability within ER+ breast cancer patients stratified by highest (red, n = 318) and lowest (black, n = 169) ER Regulon Activity signature. ER Signature was composed by addition of z-score transformed single-sample regulon values as follows (KDM4B+CCNH-SUV39H2-YEATS2). P-value determined by log-rank test and gene expression data retrieved and filtered by UCSC Xena Functional Genomics Explorer

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