Figure 7. Defects in RNA Splicing and MYC Amplification Associate with Immune Response in Human Breast Cancer.
(A) Intron retention (IR) correlates with signatures of immune infiltration in human breast cancer. Scores from ssGSEA analysis of immune cell gene signatures were computed and correlated to IR levels in BRCA tumors (n=983) in TCGA. Heatmaps show IR level across tumors and ssGSEA scores for signatures that have Pearson correlation q-value of <0.01, ranked by q-value. Subset heatmaps show tumors with IR level >1 z-score from the mean.
(B) Immune-related gene sets are enriched in tumors with high IR. GSEA with MSigDB C2 Canonical Pathways was used to compare gene expression of tumors with high vs. low IR (>1 z-score from mean). Bar plot of NES of positively enriched gene sets (FDR <0.01). Red indicates immune-related gene set.
(C) Tumors with high IR have improved disease-free survival (DFS). Kaplan-Meier plot shows DFS for patients with breast tumors (TCGA). High IR tumors have improved DFS (p=0.026, log-rank test).
(D, E) MYC-amplified breast tumors exhibit increased IR-associated immune signaling pathway activity. GSEA was used to compare gene expression patterns of human tumors divided into cohorts based on IR levels and MYC amplification. (D) Pie charts represent the percent of immune-related pathways among the top 10 enriched pathways ranked by NES. In the High IR, High MYC cohort, 7 of 10 pathways are related to immune signaling. (E) In comparison, CCNE1 amplified tumors do not exhibit increased IR-associated immune signaling.