Fig. 7
Validation of key concepts using the LNCaP–iSlug model. a GSEA enrichment plots of the “Hallmark” EMT signature (MSigDB [14]) within the transcriptional program regulated by 5 days of Dox treatment (EMT5), compared to untreated cells (No Dox; top panel), and compared to 20 days of Dox removal (MErT20). NES normalised enrichment score, FDR false discovery rate. b Scatter plots showing the Slug-derived MErTGES score in samples of localised and metastatic PCa from the bi; Grasso [23]; and bii; Taylor [25] datasets. Error bars indicate SEM. **** p < 0.0001; unpaired t-test. c Transcriptional clusters representing persistent transcript alterations. Cluster XI shows transcripts that remained upregulated and Cluster XII shows transcripts that remained downregulated during the 20 day MErT. Cluster XIII shows transcripts that were unaltered during EMT (E5) and then became newly activated by 3 days of MErT (M3) and remained for 5 and 20 days (M3, 5–20). Cluster XIV shows transcripts that were unaltered during EMT (E5) and then became newly repressed by 3 days of MErT (M3) and remained for 5 and 20 days (M5–20). Cluster avg is the average transcriptional pattern of the transcript cluster. d Enrichment score of the (di) EMT persistent (Clusters XI/XII combined) and (dii) MErT unique (Clusters XIII/XIV combined) signatures in samples of localised PCa and mCRPC from the Grasso dataset [23]. e Correlation plot of the EMT persistent and MErT unique signature scores in (ei) localised PCa and mCRPC samples (eii), and benign prostate tissue from the Grasso dataset. Error bars indicate SEM. ****, p < 0.0001; unpaired t-test. f Kaplan–Meier curves showing (fi) prostate (Setlur [33]), (fii) breast (van’t Veer [38]), and (fiii) lung (Lee [40]) cancer patient cohorts stratified according to a positive (+ve, red line) or negative (−ve, blue line) MPS score. The p-values shown are from log-rank tests comparing the two Kaplan–Meier curves
