Fig. 3: BL intra-tumor heterogeneity reflects similarities with distinct normal GC subpopulations.

A UMAP projection and cluster identification using sc-transcriptomic profiles of 21,649 BL tumor cells. B Relative gene expression displayed as UMAP/heatmap with colors representing the z-scored log2 normalized expression. C Pathway enrichment analysis for the gene signatures (top 100 upregulated) associated with the clusters identified in (A). Relevant pathways from KEGG (KG) and Hallmark (HM) databases that are significantly enriched (hypergeometric test with Benjamini-Hochberg correction, q < 0.05) are shown in gray. D UMAP projection of BL tumor cells as displayed in (A) and colored based on the highest correlation of each cluster with previously reported signatures of normal GC B cell subpopulations [9]. DZ dark zone, INT intermediate, LZ light zone, PreM memory precursors. E Heat map displaying a subset of differentially expressed genes in the subgroups identified in (D). The color bars on the left indicate genes associated with the DZ (blue), LZ (red) or PreM (yellow) signatures. The size of the dot indicates the percentage of cells with detectable expression, and the color shows the z-scored average (log2) normalized expression within a group. Box and Whisker plots displaying the distribution across the GC-related subgroups of BL tumor cells stratified by: F sample origin (E effusion, N nodal); G response to therapy (NR non-responders, R responders). A Mann-Whitney U Test was used to compare data sets pairwise (*p < 0.05).