Fig. 6

Multi-omics subtypes of PDAC patients. A Consensus-clustering analysis of proteomic profiling identifying three proteomic subtypes: S-I (blue, n = 57), S-II (pink, n = 106) and S-III (yellow, n = 54). The associations of proteomic subtypes with mutation information and clinical characteristics are annotated in the middle panel. The heatmap depicts the relative abundance of signature proteins (bottom). B The association of three proteomic subtypes with clinical outcomes in 217 PDAC samples (log-rank test). OS, overall survival; DFS, disease free survival. C Gene Ontology (GO) terms enriched in the three proteomic subtypes. D, E Spearman-rank correlation of CNA and protein that highly expressed in S-III. The significant correlations are colored in pink, and prognostic related proteins are labeled with purple circles (D). The cis-effect of GRB7 among CNA and protein is shown in (E). F P values for the correlation between IRF6 protein expression and prognosis in six kinds of gastrointestinal tumors in TCGA data. G Spearman-rank correlation of the abundance of GRB7 protein and GSVA score. Pink, cell cycle; purple, ERBB signaling pathway; blue, apoptosis. H The Venn plot on the left depicting the activated kinases in S-III and heatmaps on the right showing the global abundance and the kinase activity score of these selected kinases. For each kinase, the P value of its global abundance and kinase activity among three subtypes are shown in the center panel. I Spearman-rank correlation of the abundance of GRB7 and AKT2. J The boxplot indicating the comparison of kinase activity of AKT2 among three subtypes (one-way ANOVA). K Spearman-rank correlation of the abundance of AKT2 and GSVA score of cell cycle. L Scatter plot displaying the association between each phosphosites’ abundance with the global abundance of AKT2 (y axis) versus the global abundance of GRB7 (x axis). Cell cycle-associated phosphosites are labeled in pink. M The scatter plot indicating the cell lines with higher level of GRB7 protein expressions are more sensitive to ERBB2 inhibitor treatment (lower IC50) (Spearman’s correlation). N The bar plot indicating the frequency of pancreatic head (H-PDAC) and pancreatic body and tail (BT-PDAC) among three subtypes (Fisher’s exact test). O The heatmap indicating the GSVA scores of the pathway between H-PDAC and BT-PDAC in proteome and phosphoproteome levels. Each column represented a patient sample, color of each cell showed GSVA scores. P, Q The boxplot indicating the comparison of abundance of GRB7 (P) and MGPS (Q) score between H-PDAC and BT-PDAC (Student’s t test). R The heatmap indicating the cascading expression patterns of ERBB2, GRB7, and cell cycle related genes between tumor locations. The hazard ratios of these proteins are showed on the right. S Illustration of the regulatory role of GRB7 amplification. ****p < 1.0E−4, ***p < 1.0E−3, **p < 1.0E−2, *p < 0.05, ns > 0.05