Fig. 2: Transcriptomic features associated with response and resistance in the SU2C-MARK cohort.
a, Volcano plot of limma voom results for top response-associated genes from RNA-seq samples in the SU2C-MARK cohort (n = 152 RNA samples). Nominal P values from two-sided significance testing are shown. Cutoffs of absolute log2(fold change) > 0.5 and P < 0.05 were used to identify significantly differentially expressed genes (red). b, Hallmark GSEA of response and resistance-associated pathways from limma voom. c, Dot plot of significance values for interferon-gamma (IFN-γ) targets (n = 198 genes), proteasome subunits (n = 56 genes) and immunoproteasome subunits (n = 5 genes). Boxplot overlay depicts the 25th percentile (minima), 50th percentile (center) and 75th percentile (maxima) of distribution with whiskers bounding points within 1.5× interquartile range (Q3–Q1) from each minimum and maximum. Immunoproteasome subunits as a set showed a greater association with response than IFN-γ targets and proteasome targets (P = 7 × 10−9 and P = 4 × 10−6, respectively, two-sided Mann–Whitney U test). d, Contour plot of a linear, 2D model predicting expression of representative immunoproteasome subunit PSMB8 as a function of the inflammatory cytokines IFNG and TNF. Contour levels correspond to roughly 1.2-fold TPM increments in PSMB8 expression. Patients with high expression of both IFNG and TNF demonstrated the highest PSMB8 expression (R2 = 0.31). e, Logistic regression summary results for tumor-associated immune cell signatures derived from single-cell sequencing37.
