Fig. 4: The differential expression of proteins and signaling pathways in sensitive and non-sensitive groups of therapy subcohorts.

a The association of MSI/MSS-sig level with OS in DOS and XELOX subcohorts (two-sided log rank test). b Bubble plot showing the KEGG pathway enrichment (two-sided Fisher’s exact test) of DSG, DNSG, XSG, and XNSG groups. c, d, k The GSEA enrichment analysis of TCR signaling pathway in DOS (c), XELOX (d, n (S) = 25, n (NS) = 20), XELOX of BPRC cohort (k), and XELOX + HER2 subcohorts, respectively (left). Boxplots show median (central line), upper and lower quartiles (box limits), 1.5× interquartile range (whiskers). The survival analysis of ssGSEA TCR signaling pathway score with OS in these subcohorts (two-sided log rank test) (right). e, f, l Heatmap illustrating significantly differential cell type compositions between sensitive and non-sensitive groups of these subcohorts (two-sided Student’s t test). g ICD prediction score of 31 anticancer drugs from NCI library. h The overlap of upregulated proteins in DSG and XNSG, and the KEGG pathway enrichment (two-sided Fisher’s exact test) of these overlapped proteins. i Cox analysis (two-sided Cox test) of the proteins involved in immune modulation and ErbB2/ErbB3 signaling pathway with disease-free survival (DFS). The little boxes indicate the DFS hazard ratios. j Dose-response curves of NCI-N87 cells after 72-h treatments with XELOX, trastuzumab, and combination of trastuzumab and XELOX. The comparison of IC50 values of different therapies (two-sided Student’s t test). Bars represent the mean of n = 3 independent experiments with error bars indicating SD. m The qualification of CD4 and CD8 stained by immunohistochemistry (IHC) in representative examples in the XELOX and XELOX + HER2 subcohorts. Data are analyzed by two-sided Student’s t test and shown as mean ± SD (n = 3 independent experiments). n Diagram showing the potential connection of immune characteristics and the therapy response. Source data are provided as a Source Data file.