Extended Data Fig. 8: HuMo cluster 1 tumours display immune-paucity whilst a representative HuMo cluster 1 model displays mild inter-tumoural heterogeneity.
From: Human-correlated genetic models identify precision therapy for liver cancer
(a) Percentage (total number) of human TCGA HCC samples with mutations in CTNNB1 associated with each HuMo cluster. (b) Ratio of wild type and mutated CTNNB1 in human TCGA HCC samples within each HuMo cluster. (c) Immune-pathway analysis shows a clear association of HuMo cluster 1 with immune paucity, whereas HuMo cluster 2 shows the highest association with immune-cell enrichment. (d + e). Correlation analysis of immune score, fibroblast, and endothelial signatures with HuMo clusters and mutations in human (d) and mouse (e) emphasizes the negative enrichment for immune score in HuMo cluster 1 and CTNNB1 mutated samples in both species. (f) Summary of cohorts used in this figure; cohort 5 = BM. All mice used in this figure were male. (g) Experimental scheme for samples used in h + i. (h) Heatmap of differentially expressed genes between liver tissue from mice with global hepatocyte induction of altered genes and, non-tumour and tumour, tissue from mice with clonal hepatocyte induction of altered genes. Tumour tissue, despite induction of the same genetic alterations, differs greatly from the global induction group suggesting evolution of induced clones to develop tumours. n = 3 (global and non-tumour), 6 mice with up to 3 tumour samples per mouse (tumour). (i) Gene Ontology over-representation analysis shows upregulation of biological processes associated with oncogenesis in tumour tissue. One-sided Fisher’s exact test; adjusted using the Benjamini-Hochberg procedure.
