Fig. 3
Correlation between steady-state protein and mRNA abundance in breast tumors and association with subtypes and survival. a Density plot showing the global Spearman correlation for protein-mRNA pairs within breast tumors (n = 59; 5677 protein-mRNA pairs) and adjacent non-cancerous tissue (n = 38; 3316 pairs). Protein and mRNA abundance was positively correlated in all tissues samples with a mean Spearman’s correlation coefficient (rho) of 0.31 in tumors, which was significantly higher (P = 1.5 × 10−14, Wilcoxon rank sum test) than the rho of 0.19 in adjacent non-cancerous tissues. b Protein-mRNA pairs have considerably different global correlations among breast cancer subtypes (triple-negative, basal-like, HER2, and luminal A). Triple-negative tumors (TNBC) and tumors of the basal-like subtype (Basal) had the highest mean correlation while luminal A tumors (LumA) had the lowest correlation. c Concordance between protein and transcript levels varies by tumor grade. Poorly differentiated grade III tumors had the highest mean correlation between protein and mRNA pairs. b, c P values were calculated using the Kruskal Wallis test. d, e Estrogen receptor (ER)-negative tumors and tumors from African-American patients show an increased concordance between protein and mRNA abundance. f Global protein-mRNA concordance values closely correlate with the proliferation score in the 59 tumors (r = 0.7; P = 8 × 10−10, Pearson correlation) but not in the 38 adjacent non-cancerous tissues (g). The dashed line shows regression. h High concordance between protein-mRNA pairs in tumors is associated with decreased breast cancer survival. Tumors were stratified into three groups according to their global correlation coefficient across all protein-mRNA pairs [< 25%, 25–75%, and > 75% (tumors with highest global correlation)]. Shown is a Kaplan-Meier plot for these three groups. Tumors with the highest correlations between protein and mRNA pairs had the worst outcome [Cox regression hazard ratio (HR) comparing 75% vs. 25% tumor group = 6.91, 95% CI 1.5–31.7 adjusted for disease subtypes; Ptrend across the three groups = 0.004]