Fig. 6

Differential gene expression (DGE) analysis of HLBC subsets. A, B Inter-group DGE analysis with the HER2-positive (A) and with HER2-negative (B) carcinomas as a reference. The heatmap reports the GSS as a variable: blue pathways with no differential expression and orange those with high differential expression. C Heatmap of the dGSS, reporting the polarization (up or down) of differential expression (HER2-positive as the reference group). D Volcano plots reporting the DE genes between HER2-negative and HLBCs versus HER2-positive tumors. On the y-axis, we reported the -log10 of the P-value (ANOVA model, FDR-adjusted), and on the x-axis, the log2 fold change. Red squares represent the ERBB2 and GRB7 gene expression. E, F Inter-group DGE analysis after stratification for HER2 subgroups (HER2-positive carcinomas as a reference in E and HER2-negative as a reference in F). The heatmap reports the GSS as a variable: blue pathways with no differential expression and orange those with high differential expression. G, H Inter-HLBC DGE analysis, with HLBC-1 class as reference and HLBC-2N (G) or HLBC-2E (F) as a target. The y-axis reports the gene sets (NanoString private algorithm), and x-axis reports the differential expression means (95%CI) between response variables (unadjusted scale). The dashed vertical axis is shown at fold change equal to zero, indicating equivalent expression between the groups. A signature is considered significant if the 95%CI (the horizontal line) does not cross the vertical axis representing the baseline group and therefore no difference to that baseline group. Dark green triangles marked the differentially expressed gene sets